J.J. Secades de colina y biosíntesis de fosfolípidos. In De la Morena E, 89. Wong JT, Chan M, Lee D, Jiang JY, Skrzypczak M, Choy PC. ed. Citicolina: bioquímica, neurofarmacología y clínica. Phosphatidylcholine metabolism in human endothelial cells: Barcelona: Salvat; 1985. p. 2538. modulation by phosphocholine. Mol Cell Biochem 2000; 207: 72. Chida N, Shimizu Y. Biosynthesis of myelin lipids of cultured 95100. nervous tissues. Incorporation of choline and CDPcholine 90. Lykidis A, Jackson P, Jackowski S. Lipid activation of CTP: into myelin phospholipids. Tohoku J Exp Med 1973; 111: 419. phosphocholine cytidylyltransferase α: characterization and 73. Marggraf WD, Anderer FA. Alternative pathways in the identification of a second activation domain. Biochemistry biosynthesis of sphingomyelin and the role of phosphatidyl 2001; 40: 494503. choline, CDPcholine and phosp horylcholine as precursors. 91. FernándezTome MC, Speziale EH, SterinSpeziale NB. Hoppe Seylers Z Physiol Chem 1974; 355: 80310. Phospholipase C inhibitors and prostaglandins differentially 74. Vance DE, Pelech SL. Cellular translocation of CTP: regulate phosphatidylcholine synthesis in rat renal papilla. phosphocholine cytidylyltransferase regulates the synthesis Evidence of compartmental regulation of CTP:phosphocholine of CDPcholine. In Zappia V, Kennedy EP, Nilsson BI, Galletti cytidylyltransferase and CDPcholine:1,2diacylglycerol P, eds. Novel biochemi cal, pharmacological and clinical cholinephosphotransferase. Biochim Biophys Acta 2002; aspects of cytidinediphosphocholine. Amsterdam: Elsevier 1583: 18594. Science Publishing; 1985. p. 1524. 92. Lagace TA, Ridgway ND. The ratelimiting enzyme in 75. Goracci G, Francescangeli E, Mozzi R, Porcellati S, Porcellati phosphatidylcholine synthesis regulates proliferation of the G. Regulation of phospholipid metabolism by nucleotides in nucleoplasmic reticulum. Mol Biol Cell 2005; 16: 112030. brain and transport of CDPcholine into brain. In Zappia V, 93. Satoh N, Harada A, Yokoyama K, Karasawa K, Inoue K, Kennedy EP, Nilsson BI, Galletti P, eds. Novel biochemi cal, Setaka M. Regulation of activities of cytidine 5’diphospho pharmacological and clinical aspects of cytidinedilphospho choline: 1Oalkyl2acetylsnglycerol cholinephospho choline. Amsterdam: Elsevier Science Publishing; 1985. transferase, an enzyme respondible for de novo synthesis p. 10516. of plateletactivating factor, by membrane phospholipids. 76. George TP, Cook HW, Byers DM, Palmer FB, Spence MW. J Health Sci 2003; 49: 1321. Channeling of intermediates in the CDPcholine pathway 94. Richardson UI, Watkins CJ, Pierre C, Ulms IH, Wurtman RJ. of phosphatidylcholine biosynthesis in cultured glioma cells Stimulation of CDPcholine synthesis by uridine or cytidine is dependent on intracellular Ca . J Biol Chem 1991; 266: in PC12 rat pheochromocytoma cells. Brain Res 2003; 971: 2+ 1241923. 1617. 77. Murphy EJ, Horrocks LA. CDPcholine, CDPethanolamine, 95. Zaccheo O, Dinsdale D, Meacock PA, Glynn P. Neuropathy lipid metabolism and disorders of the central nervous system. target esterase and its yeast homologue degrade phosphatidyl In Massarelli R, Horrocks LA, Kanfer JN, Löffelholz K, eds. choline to glycerophosphocholine in living cells. J Biol Chem Phospholipids and signal transmission. Berlin: SpringerVerlag; 2004; 279: 2402433. 1993. p. 35372. 96. Horrocks LA, Dorman RV. Prevention by CDPcholine and 78. Tronchère H, Record M, Tercé F, Chap H. Phosphatidylcholine CDPethanolamine of lipid changes during brain ischemia. cycle and regulation of phosphatidylcholine biosynthesis In Zappia V, Kennedy EP, Nilsson BI, Galletti P, eds. Novel by enzyme translocation. Biochim Biophys Acta 1994; 1212: biochemical, pharmacological and clinical aspects of 13751. cytidinediphosphocholine. Amsterdam: Elsevier Science 79. Weiss GB. Metabolism and actions of CDPcholine as Publishing; 1985. p. 20515. an endogenous compound and administered exogenously 97. Le PoncinLafitte M, Duterte D, Lageron A, Rapin JR. as citicoline. Life Sci 1995; 56: 63760. CDPcholine et accident cérébral expérimental d’origine 80. Jackowski S, Wang J, Baburina I. Activity of the phosphatidyl vasculaire. Agressologie 1986; 27: 4136. choline biosynthetic pathway modulates the distribution of 98. Mykita S, Golly F, Dreyfus H, Freysz L, Massarelli R. Effect of fatty acids into glycerolipids in proliferating cells. Biochim CDPcholine on hypocapnic neurons in culture. J Neurochem Biophys Acta 2000; 1483: 30115. 1986; 47: 22331. 81. Dowd SR, Bier ME, PattonVogt JL. Turnover of phosphatidyl 99. Yasuhara M, Naito H. Characteristic actions of CDPcholine choline in Saccharomyces cerevisae. The role of the CDP on the central nervous system. Cur Ther Res Clin Exp1974; choline pathway. J Biol Chem 2001; 276: 375663. 16: 34674. 82. Henneberry AL, Wright MM, McMaster CR. The major 100. Yasuhara M, Naito H, Tachibana Y, Yasuhara A. An electro sites of cellular phospholipid synthesis and molecular physiological study on the effects of CDPcholine in the determinants of fatty acid and lipid head group specificity. central nervous system. In Zappia V, Kennedy EP, Nilsson Mol Biol Cell 2002; 13: 314861. BI, Galletti P, eds. Novel biochemical, pharmacological and 83. Hunt AN, Clark GT, Neale JR, Postle AD. A comparison of clinical aspects of cytidinediphosphocholine. Amsterdam: the molecular specificities of whole cell and endonuclear Elsevier Science Publishing; 1985. p. 25974. phosphatidylcholine synthesis. FEBS Lett 2002; 530: 8993. 101. MartíViaño JL, Selles J, Orts A, Marco J, Vega F, Esplugues J. 84. Kulinski A, Vance DE, Vance JE. A cholinedeficient diet in Antagonismo del coma barbitúrico mediante productos mice inhibits neither the CDPcholine pathway for phospha alertizantes. Estudio experimen tal. Rev Esp Anestesiol tidylcholine synthesis in hepatocytes nor apolipoprotein B Reanim 1978; 25: 218. secretion. J Biol Chem 2004; 279: 2391624. 102. Ogashiwa M, Sano K, Manaka S, Kitamura K, Kagawa M, 85. Li Z, Vance DE. Phosphatidylcholine and choline homeostasis. Takeuchi K. Effectiveness of CDPcholine on disturbance J Lipid Res 2008; 49: 118794. of consciousness (DOC): 1. An experimental study of 86. Arienti G, Corazzi L, Mastrofini P, Montanini I, Trillini B, concussive head injury in mice. 2. A controlled trial in Porcellati G. Involvement of CDPcholine in phospholipid patients with DOC. In Zappia V, Kennedy EP, Nilsson BI, metabolism of brain tissue in vitro. Ital J Biochem 1979; 28: Galletti P, eds. Novel biochemical, pharmacological and 3945. clinical aspects of cytidinediphosphocholine. Amsterdam: 87. Jané F. Algunos aspectos de la farmacología de la citicolina. Elsevier Science Publishing; 1985. p. 31727. In De la Morena E, ed. Citicolina: bioquímica, neurofarma 103. Watanabe S, Kono S, Nakashima Y, Mitsunobu K, Otsuki S. cología y clínica. Barcelona: Salvat; 1985. p. 4962. Effects of various cerebral metabolic activators on glucose 88. Clement JM, Kent C. CTP:phosphocholine cytidylyl metabolism of brain. Folia Psychiatr Neurol Jpn 1975; 29: transferase: insights into regulatory mechanisms and novel 6776. functions. Biochem Biophys Res Commun 1999; 257: 64350. 104. Arrigoni E, Averet N, Cohadon F. Effects of CDPcholine on S50 www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62
Citicolina: revisión farmacológica y clínica, actualización 2010 phospholipase A and cholinephosphotransferase activities 122. Baskaya MK, Dogan A, Rao AM, Dempsey RJ. Neuroprotective 2 following a cryogenic brain injury in the rabbit. Biochem effects of citicoline on brain edema and bloodbrain barrier Pharmacol 1987; 36: 3697700. breakdown after traumatic brain injury. J Neurosurg 2000; 105. Freysz L, Golly F, Mykita S, Avola R, Dreyfus H, Massarelli R. 92: 44852. Metabo lism of neuronal cell culture: modifications induced 123. Dempsey RJ, Raghavendra Rao VL. Cytidinediphosphocholine by CDPcholine. In Zappia V, Kennedy EP, Nilsson BI, treatment to decrease traumatic brain injuryinduced Galletti P, eds. Novel biochemical, pharmacological and hippocampal neuronal death, cortical contusion volume, clinical aspects of cytidinediphosphocholine. Amsterdam: and neurological dysfunction in rats. J Neurosurg 2003; 98: Elsevier Science Publishing; 1985. p. 11725. 86773. 106. Massarelli R, Mozzi R, Golly F, Hattori H, Dainous F, Kanfer 124. Menku A, Ogden M, Saraymen R. The protective effects of JN, et al. Synthesis de novo of choline, production of choline propofol and citicoline combination in experimental head from phospholipids, and effects of CDPcholine on nerve injury in rats. Turk Neurosurg 2010; 20: 5762. cell survival. Fidia Res Ser 1986; 4: 27381. 125. Cakir E, Usul H, Peksoylu B, Sayin OC, Alver A, Topbas M, 107. Kitazaki T, Ohta Y, Tsuda M. Inhibition of membrane et al. Effects of citicoline on experimental spinal cord injury. associated phospholipase A by CDPcholine. Jpn Pharmacol J Clin Neurosci 2005; 12: 9247. 2 Ther 1985; 13: 15964. 126. Yucel N, Cayli SR, Ates O, Karadag N, Firat S, Turkoz Y. 108. Farooqui AA, Litsky ML, Farooqui T, Horrocks LA. Evaluation of the neuroprotective effects of citicoline after Inhibitors of intracellular phospholipase A2 activity: their experimental spinal cord injury: improved behavioral and neurochemical effects and therapeutical importance for neuroanatomical recovery. Neurochem Res 2006; 31: 76775. neurological disorders. Brain Res Bull 1999; 49: 13953. 127. Coskun C, Avci B, Ocak N, Yalcin M, Dirican M, Savci V. 109. Algate DR, Beard DJ, Sacristán A, Ortíz AJ, Davies JE. Study Effect of repeatedly given CDPcholine on cardiovascular on the effects of oral administration of CDPcholine on EEG and tissue injury in spinal shock conditions: investigation changes and lethality induced by epidural compression in of the acute phase. J Pharm Pharmacol 2010; 62: 497506. the anesthetised cat. Arzneimittelforschung 1983; 33: 10136. 128. Turkkan A, Alkan T, Goren B, Kocaeli H, Akar E, Korfali E. 110. Hayaishi O, Ozawa K, Araki C, Ishii S, Kondo Y. Biochemical Citicoline and postconditioning provides neuroprotection studies of head injury and brain edema. Jpn J Med Prog 1961; in a rat model of ischemic spinal cord injury. Acta Neurochir 48: 51939. (Wien) 2010; 152: 103342. 111. Kondo Y. Experimental study on the therapeutic use of 129. Schuettauf F, Rejdak R, Thaler S, Bolz S, Lehaci C, Mankowska cytidine nucleotides for brain injury. Nippon Geka Hokan A, et al. Citicoline and lithium rescue retinal ganglion cells 1963; 32: 489505. following partial optic nerve crush in the rat. Exp Eye Res 112. Tsuchida T, Nagai M, Hoshino T, Kamano S, Miyake H. 2006; 83: 112834. Treatment of head injuries with intermediate substances 130. Ozay R, Bekar A, Kocaeli H, Karli N, Filiz G, Ulus IH. of metabolic cycle of brain. II. Basic study on metabolism of Citicoline improves functional recovery, promotes nerve cytidine diphosphate choline. Brain Nerve 1967; 19: 10415. regeneration, and reduces postoperative scarring after 113. Boismare F, Le Poncin M, Le François J, Hacpille L, Marchand peripheral nerve surgery in rats. Surg Neurol 2007; 68: 61522. JC. Étude des effets de l’administration de cytidinediphospho 131. Galletti P, De Rosa M, Cotticelli MG, Morana A, Vaccaro R, choline sur les consèquences hémodynamiques, fonctionelles Zappia V. Biochemical rationale for the use of CDPcholine et biochimiques du traumatisme crâniocervical chez le rat. in traumatic brain injury: phar macokinetics of the orally Therapie 1977; 32: 34554. administered drug. J Neurol Sci 1991; 103 (Suppl): S1925. 114. Clendenon NR, Palayoor ST, Gordon WA. Influence of 132. Cohen MM. Biochemistry of cerebral anoxia, hypoxia and CDPcholine on ATPase activity in acute experimental ischemia. Monogr Neural Sci 1973; 1: 149. spinal cord trauma. In Zappia V, Kennedy EP, Nilsson BI, 133. Siesjö BK. Cell damage in the brain caused by ischemia. Galletti P, eds. Novel biochemical, pharmacological and An overview. In Krieglstein J, ed. Pharmacology of cerebral clinical aspects of cytidinediphosphocholine. Amsterdam: ischemia. Amsterdam: Elsevier Science Publishers; 1986. Elsevier Science Publishing; 1985. p. 27584. p. 311. 115. Cohadon F, Richer E, Poletto B. Étude d’un précurseur des 134. Porcellati G, De Medio GE, Fini C, Floridi A, Goracci G, phospholipides dans le traitement des comas traumatiques Horrocks LA, et al. Phospholipids and its metabolism in graves. Neurochirurgie 1982; 28: 28790. ischemia. Proc Eur Soc Neurochem 1978; 1: 285302. 116. Lafuente JV, CervósNavarro J. Estudio por microgavimetría 135. Boismare F, Le PoncinLafitte M, Rapin JR. Effets hémo del efecto de la CDPcolina en el edema cerebral experimental dynamiques, fonctione lles et biochimiques de l’hypoxie inducido por radiaciones ultravioletas. Med Clin (Barc) 1986; hypobare chez le rat traité par la cytidine diphospho choli ne. 87 (Supl 1): S58. C R Seances Soc Biol Fil 1978; 172: 6518. 117. CervósNavarro J, Lafuente JV. Effect of cytidine diphosphate 136. Boismare F, Le PoncinLafitte M. Influence d’un traitement choline on ultravioletinduced brain edema. Adv Neurol 1990; par la citidoline sur les effets hémodynamiques de l’hypoxie 52: 4219. normobare dans le chien. C R Seances Soc Biol Fil 1978; 172: 118. Majem X, BidónChanal A, ViláBadó J. Estudio de los efectos 65963. del tratamiento oral con CDPcolina sobre los cambios 137. Boismare F, Le Poncin M, Lefrançois J, Lecordier JC. Action inducidos por el edema encefálico experimental en el of cytidine diphosphocholine on functional and hemodynamic electroencefalograma de la rata no anestesiada. Med Clin effects of cerebral ischemia in cats. Pharmacology 1978; 17: (Barc) 1986; 87 (Supl 1): S235. 1520. 119. Roda JE. Répartition macro et microscopique d’un œdème 138. Alberghina M, Viola M, Serra I, Mistretta A, Giuffrida AM. cérébral vasogeni que experimental. In Symposium International: Effect of CDPcholine on the biosynthesis of phospholipids Souffrance Cérébrale et Précurseurs des Phospholipides. in brain regions during hypoxic treatment. J Neurosci Res París, Francia, 18 de enero de 1980. 1981; 6: 42133. 120. Dixon CE, Ma X, Marion DW. Effects of CDPcholine treatment 139. Serra I, Alberghina M, Viola M, Mistretta A, Giuffrida AM. on neurobehavioral deficits after TBI and on hippocampal and Effects of CDPcholine on the biosynthesis of nucleic acids neocortical acetylcholine release. J Neurotrauma 1997; 14: 1619. and proteins in brain regions during hypoxia. Neurochem Res 121. Plataras C, Taskiris S, Angelogianni P. Effect of CDPcholine 1981; 6: 60718. on brain acetylcholinesterase and Na+/K+ATPase in adult 140. Horrocks LA, Dorman RV, Dabrowiecki Z, Goracci G, rats. Clin Biochem 2000; 33: 3517. Porcellati G. CDPcholine and CDPethanolamine prevent www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62 S51
J.J. Secades the release of free fatty acids during brain ischemia. 159. Adibhatla RM, Hatcher JF, Tureyen K. CDPcholine Prog Lipid Res 1981; 20: 5314. liposomes provide significant reduction in infarction over 141. Trovarelli G, De Medio GE, Dorman RV, Piccinin GL, free CDPcholine in stroke. Brain Res 2005; 1058: 1937. Horrocks LA, Porcellati G. Effect of cytidine diphosphate 160. Tornos ME, Sacristán A, Ortiz JA. Pharmacological study choline (CDPcholine) on ischemiainduced alterations of CDPcholine. Protection against toxicity in a model of brain lipid in the gerbil. Neurochem Res 1981; 6: 82133. of experimental hypoxia. Arzneimittelforschung 1983; 33: 142. Trovarelli G, De Medio GE, Montanini I. The influence of 10224. CDPcholine on brain lipid metabolism during ischemia. 161. Benzi G, Pastoris O, Villa RF. Pharmacobiological Farmaco Sci 1982; 37: 6638. interventions of CDPcholine in hypoxia and aging of the 143. Dorman RV, Dabrowiecki Z, Horrocks LA. Effects of CDP brain. In Zappia V, Kennedy EP, Nilsson BI, Galletti P, eds. choline and CDPethanolamine on the alterations in rat brain Novel biochemical, pharmacological and clinical aspects lipid metabolism induced by global ischemia. J Neurochem of cytidinediphosphocholine. Amsterdam: Elsevier Science 1983; 40: 2769. Publishing; 1985. p. 23949. 144. Suno M, Nagaoka A. Effect of CDPcholine on cerebral lipid 162. Villa RF, Curti D, Polgatti M, Benzi G. Synaptosomes metabolism following complete ischemia in rats. Yakuri to and mitochondria from rat brain cerebral cortex: in vivo Chiryo 1985; 13: 16570. interference on some enzymatic activities by SAMe and 145. Murphy EJ, Horrocks LA. Mechanism of action of CDP CDPcholine. J Neurosci Res 1982; 7: 3417. choline and CDPetha nolamine on fatty acid release during 163. Narumi S, Nagaoka A. Effects of CDPcholine on the ischemia of brain. In Bazan NG, ed. New trends in lipid metabolism of monoa mines in the brain of rats with mediators research. Vol. 4. Lipid mediators in ischemic brain experimental cerebral ischemia. Jpn Pharmacol Ther 1985; damage and experimental epilepsy. Basilea: Karger; 1990. 13: 1718. p. 6784. 164. Nagai Y, Nagaoka A. Effect of CDPcholine on glucose 146. Agut J, Ortiz JA. Effect of oral cytidine(5’)diphosphocholine uptake into various brain regions in the cerebral ischemic (CDPcholine) administration on the metabolism of rats. Jpn Pharmacol Ther 1985; 13: 2359. phospholipids in rat brain during normobaric hypoxia. 165. Hurtado O, Moro MA, Cárdenas A, Sánchez V, Fernández In Wurtman R, Corkin SH, Growdon JH, eds. Alzheimer’s Tome P, Leza JC, et al. Neuroprotection afforded by prior disease: advances in basic research and therapies. Cambridge: citicoline administration in experimental brain ischemia: Center for Brain Sciences and Metabolism Charitable Trust; effects on glutamate transport. Neurobiol Dis 2005; 18: 33645. 1987. p. 32732. 166. Hurtado O, Pradillo JM, FernándezLópez D, Morales JR, 147. D’Orlando KJ, Sandage BW. Citicoline (CDPcholine): Sobrino T, Castillo J, et al. Delayed postischemic administration mechanisms of action and effects in ischemic brain injury. of CDPcholine increases EAAT2 association to lipid rafts Neurol Res 1995; 17: 2814. and affords neuroprotection in experimental stroke. Neurobiol 148. López GonzálezCoviella I, Clark WM, Warach S, Sandage Dis 2008; 29: 12331. B, Agut J, Ortiz JA, et al. CDPcholine (citicoline): potential 167. Hurtado O, Cárdenas A, Pradillo JM, Morales JR, Ortego F, mechanism of action and preliminary results in human stroke. Sobrino T, et al. A chronic treatment with CDPcholine In Goldstein LB, ed. Restorative neurology: advances in improves functional recovery and increases neuronal plasticity pharmacotherapy. Armonk, New York: Futura Publishing; after experimental stroke. Neurobiol Dis 2007; 26: 10511. 1998. p. 195212. 168. Zhao JJ, Liu Y, Chen XL, Liu JX, Tian YF, Zhang PB, et al. 149. AbadSantos F, GallegoSandín S, Novalbos J, GálvezMúgica Effect of citicoline on spatial learning and memory of rats MA. Estado actual de la citicolina en la isquemia cerebral. after focal cerebral ischemia. Nan Fang Yi Ke Da Xue Xue Rev Neurol 2000; 30: 66370. Bao 2006; 26: 1746. 150. Rao AM, Hatcher JF, Dempsey RJ. CDPcholine: 169. Kakihana M, Kato J, Narumi S, Nagaoka A. CDPcholine: neuroprotection in transient forebrain ischemia of gerbils. Distribution of radioactive CDPcholine and effect on glucose J Neurosci Res 1999; 58: 697705. metabolism in the cerebral cortex of rats with 30min cerebral 151. Rao AM, Hatcher JF, Dempsey RJ. Lipid alterations in transient ischemia. Jpn Pharmacol Ther 1985; 13: 24153. forebrain ischemia: Possible new mechanisms of CDP 170. Kakihana M, Fukuda N, Suno M, Nagaoka A. Effects of choline neuroprotection. J Neurochem 2000; 75: 252835. CDPcholine on neurologic deficits and cerebral glucose 152. Adibhatla RM, Hatcher JF, Dempsey RJ. Citicoline: metabolism in a rat model of cerebral ischemia. Stroke 1988; neuro protective mechanisms in cerebral ischemia. J Neurochem 19: 21722. 2002; 80: 1223. 171. Fukuda N, Ikeda K, Saji Y. Effects of CDPcholine in the rats 153. Adibhatla RM, Hatcher JF. Citicoline mechanisms and clinical with experimen tal cerebral ischemia. Jpn Pharmacol Ther efficacy in cerebral ischemia. J Neurosci Res 2002; 70: 1339. 1985; 13: 21927. 154. Adibhatla RM, Hatcher J.F. Citicoline decreases phospholipase 172. Nagaoka A. Effects of CDPcholine on neurological deficits A stimulation and hydroxyl radical generation in transient in strokeprone spontaneously hypertensive rats with 2 cerebral ischemia. J Neurosci Res 2003; 73: 30815. experimental cerebral ischemia. Jpn Pharmacol Ther 1985; 155. Adibhatla RM, Hatcher JF, Dempsey RJ. Phospholipase A , 13: 229234. 2 hydroxyl radicals, and lipid peroxidation in transient 173. Saligaut C, Boismare F. Tratamiento oral crónico con cerebral ischemia. Antoxid Redox Signal 2003; 5: 64754. citidín(5’)difosfocolina de los efectos sobre el comportamiento 156. Adibhatla RM, Hatcher JF. Cytidine 5’diphosphocholine y bioquímicos de una hipoxia. Med Clin (Barc); 87 (Supl 1): (CDPcholine) in stroke and other CNS disorders. S1922. Neurochem Res 2005; 30: 1523. 174. Barrachina M, Domínguez I, Ambrosio S, Secades J, Lozano 157. Adibhatla RM, Hatcher JF, Dempsey RJ. Cytidine5’ R, Ferrer I. Neuroprotective effect of citicoline in 6hydroxy diphosphocholine affects CTPphosphocholine cytidylyl dopaminelesioned rats and in 6hydroxydopaminetreated transferase and lysophosphatidylcholine after transient SHSY5Y human neuroblastoma cells. J Neurol Sci 2003; 215: brain ischemia. J Neurosci Res 2004; 76: 3906. 10510. 158. Adibhatla RM, Hatcher JF, Larsen EC, Chen X, Sun D, Tsao 175. Araki H, Karasawa Y, Nojiri M, Aihara H. Effect of various FH. CDPcholine significantly restores phosphatidylcholine classes of drugs on complete ischemia induced by decapitation levels by differentially affecting phospholipase A and and cyanide intoxication in mice. Methods Find Exp Clin 2 CTP:phosphocholine cytidylytransferase after stroke. Pharmacol 1988; 10: 34956. J Biol Chem 2006; 281: 671825. 176. Aronowski J, Strong R, Grotta JC. Citicoline for treatment S52 www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62
Citicolina: revisión farmacológica y clínica, actualización 2010 of experimental focal ischemia: histologic and behavioral et al. Action of citicoline on rat retinal expression of extra outcome. Neurol Res 1996; 18: 5704. cellularsignalregulated kinase (ERK1/2). Brain Res 2006; 177. Schäbitz WR, Weber J, Takano K, Sandage BW, Locke KW, 1081: 20310. Fisher M. The effects of prolonged treatment with citicoline 196. Park CH, Kim YS, Lee HK, Kim YH, Choi MY, Jung DE, et in temporary experimental focal ischemia. J Neurol Sci 1996; al. Citicoline reduces upregulated clusterin following kainic 138: 215. acid injection in the rat retina. Curr Eye Res 2007; 32: 105563. 178. Andersen M, Overgaard K, Meden P, Boysen G, Choi SC. 197. Hamdorf G, CervósNavarro J. Study of the effects of oral Effects of citicoline combined with thrombolytic therapy administration of CDPcholine on openfield behaviour under in a rat embolic stroke model. Stroke 1999; 30: 146471. conditions of chronic hypoxia. Arzneimittelforschung 1990; 179. DíezTejedor E, Gutiérrez M, Carceller F, Roda JM, Alonso 40: 51922. M. Treatment with reperfussion and neuroprotection with 198. Hamdorf G, CervósNavarro J. Therapeutic effect of orally low and high dose of citicoline in an experimental model applied cytidine diphosphate choline in mild and severe of focal cerebral ischemia. Which is the best? In 5th WSC. degrees of normobaric and normocapnic degrees of hypoxia Vancouver, Canadá, 2004. of rats. Arzneimittelforschung 1991; 41: 120610. 180. Alonso de Leciñana M, Gutiérrez M, Roda JM, Carceller F, 199. Lee HJ, Kang JS, Kim YI. Citicoline protects against cognitive DíezTejedor E. Effect of combined therapy with thrombolysis impairment in a rat model of chronic cerebral hypoperfusion. and citicoline in a rat model of embolic stroke. J Neurol Sci J Clin Neurol 2009; 5: 338. 2006; 247: 1219. 200. Masi I, Giani E, Galli C. Effects of CDPcholine on platelet 181. Shuaib A, Yang Y, Li Q. Evaluating the efficacy of citicoline aggregation and the antiaggregatory activity of arterial wall in embolic ischemic stroke in rats: neuroprotective effects in the rat. Pharmacol Res Commun 1986; 18: 27381. when used alone or in combination with urokinase. 201. Pinardi G, Pelissier T, Kramer V, Paeile C, Miranda HF. Exp Neurol 2000; 161: 7339. Effects of CDPcholine on acetylcholineinduced relaxation 182. Önal MZ, Li F, Tatlisumak T, Locke KW, Sandage BW, of the perfused carotid vascular beds of the rat. Gen Pharmacol Fisher M. Synergistic effects of citicoline and MK801 in 1994; 25: 6358. temporary experimental focal ischemia in rats. Stroke 1997; 202. Clark W, GunionRinker L, Lessov N, Hazel K. Citicoline 28: 10605. treatment for experimental intracerebral hemorrhage in 183. Schäbitz WR, Li F, Irie K, Sandage BW, Locke KW, Fisher mice. Stroke 1998; 29: 213640. M. Synergistic effects of a combination of lowdose basic 203. Kermer P, Klocker N, Bahr M. Neuronal death after brain fibroblast growth factor and citicoline after temporary injury. Models, mechanisms, and therapeutic strategies experimental focal ischemia. Stroke 1999; 30: 42732. in vivo. Cell Tissue Res 1999; 298: 38395. 184. Ataus SA, Onal MZ, Ozdem SS, Locke KW, Balkan S. 204. Banasiak KJ, Xia Y, Haddad GG. Mechanisms underlying The effects of citicoline and lamotrigine alone and in hypoxiainduced neuronal apoptosis. Prog Neurobiol 2000; combination following permanent middle cerebral artery 62: 21549. occlusion in rats. Int J Neurosci 2004; 114: 18396. 205. Kuschinsky W, Gillardon F. Apoptosis and cerebral ischemia. 185. Sobrado M, López MG, Carceller F, García AG, Roda JM. Cerebrovasc Dis 2000; 110: 1659. Combined nimodipine and citicoline reduce infarct size, 206. Mattson MP, Culmsee C, Yu ZF. Apoptotic and antiapoptotic attenuate apoptosis and increase Bcl2 expression after focal mechanisms in stroke. Cell Tissue Res 2000; 301: 17387. cerebral ischemia. Neuroscience 2003; 118: 10713. 207. Harrison DC, Davis RP, Bond BC, Campbell CA, James MF, 186. Qin HZ, Wang JL, Li LH, Bai WS, Zhao ZW, Gao GD. Parsons AA, et al. Caspase mRNA expression in a rat model Neuroprotective effect of the combination of nimodipine of focal cerebral ischemia. Mol Brain Res 2001; 89: 13346. and citicoline on focal cerebral ischemiareperfusion rats. 208. Love S, Barber R, Srinivasan A, Wilcock GK. Activation of Chinese Journal of Cerebrovascular Diseases 2009; 6: 2932. caspase3 in permanent and transient brain ischaemia in man. 187. Sahin S, Alkan T, Temel SG, Tureyen K, Tolunay S, Korfali Neuroreport 2000; 11: 249599. E. Effects of citicoline used alone and in combination with 209. Love S, Barber R, Wilcock GK. Neuronal death in brain mild hypothermia on apoptosis induced by focal cerebral infarcts in man. Neuropathol Appl Neurobiol 2000; 26: 5566. ischemia in rats. J Clin Neurosci 2010; 17: 22731. 210. Krupinski J, Ferrer I, Barrachina M, Secades JJ, Mercadal J, 188. Gutiérrez M, Rodríguez B, Álvarez J, Expósito M, Vallejo M, Lozano R. CDPcholine reduces procaspase and cleaved Merino J, et al. Effects of citicoline and mesenchymal stem caspase3 expression, nuclear DNA fragmentation, and cells in acute cerebral infarct. Experimental study in rats. specific PARPcleaved products of caspase activation following In XIX European Stroke Conference. Barcelona, España, middle cerebral artery occlusion in the rat. Neuropharmacology 2528 de mayo de 2010. 2002; 42: 84654. 189. Fresta M, Puglisi G, Di Giacomo C, Russo A. Liposomes as 211. Krupinski J, Slevin M, Badimon L. Citicoline inhibits MAP invivo carriers for citicoline: effects on rat cerebral post kinase signalling pathways after focal cerebral ischaemia. ischemic reperfusion. J Pharm Pharmacol 1994; 46: 97481. Neurochem Res 2005; 30: 106773. 190. Fresta M, Puglisi G. Biological effects of CDPcholine 212. Mir C, Clotet J, Aledo R, Durany N, Argemí J, Lozano R, et loaded long circulating liposomes on rat cerebral post al. CDPcholine prevents glutamatemediated cell death in ischemic reperfusion. Int J Pharm 1996; 134: 8997. cerebellar granule neurons. J Mol Neurosci 2003; 20: 539. 191. Fresta M, Puglisi G. Survival rate improvement in a rat 213. Barrachina M, Secades J, Lozano R, GómezSantos C, ischemia model by long circulating liposomes containing Ambrosio S, Ferrer I. Citicoline increases glutathione redox cytidine5’diphosphate choline. Life Sci 1997; 61: 122735. ratio and reduces caspase3 activation and cell death in 192. Fresta M, Puglisi G. Reduction of maturation phenomenon staurosporinetreated SHSY5Y human neuroblastoma in cerebral ischemia with CDPcholineloaded liposomes. cells. Brain Res 2002; 957: 8490. Pharm Res 1999; 16: 18439. 214. Oshitari T, Fujimoto N, AdachiUsami E. Citicoline has a 193. Park CH, Kim YS, Noh HS, Cheon EW, Yang YA, Yoo JM, et protective effect on damaged retinal ganglion cells in mouse al. Neuroprotective effect of citicoline against KAinduced culture retina. Neuroreport 2002; 13: 210911. neurotoxicity in the rat retina. Exp Eye Res 2005; 81: 3508. 215. Matyja E, Taraszewska A, Naganska E, Grieb P, Rafalowska J. 194. Han YS, Chung IY, Park JM, Yu JM. Neuroprotective effect CDPcholine protects motor neurons against apoptotic of citicoline on retinal cell damage induced by kainic acid changes in a model of chronic glutamate excitotoxicity in rats. Korean J Ophthalmol 2005; 19: 21926. in vitro. Folia Neuropathol 2008; 46: 13948. 195. Park CH, Kim YS, Cheon EW, Noh HS, Cho CH, Chung IY, 216. Oshitari T, YoshidaHata N, Yamamoto S. Effect of neuro www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62 S53
J.J. Secades trophic factors on neuronal apoptosis and neurite regeneration (HVA) y 34dihidroxifenilacé tico (DOPAC) en estriado in cultured rat retinas exposed to high glucose. Brain Res de rata. Med Clin (Barc) 1986; 87 (Supl 1): S910. 2010; 1346: 4351. 234. Agut J, Font E, Sacristán A, Ortiz JA. Acción de la CDP 217. Fiedorowicz M, Makarewicz D, StanczakMrozek KI, Grieb colina sobre la hipotermia inducida por la apomorfina en P. CDPcholine (citicoline) attenuates brain damage in a rat ratas. Med Clin (Barc) 1986; 87 (Supl 1): S113. model of birth asphyxia. Acta Neurobiol Exp (Wars) 2008; 235. Agut J, Font E, Saladrich JM, Sacristán A, Ortiz JA. Acción 68: 38997. farmacológica de la CDPcolina oral en un modelo de 218. Giralt D, GarcíaBonilla L, Mendioroz M, Domingues discinesia tardía en rata. Med Clin (Barc) 1986; 87 (Supl 1): Montanari S, Rosell A, Montaner J. Effect of citicoline S148. treatment in animal models of focal cerebral ischemia: 236. Agut J, Font E, Saladrich JM, Sacristán A, Ortiz JA. Effect of a systematic review and metaanalysis. In International oral CDPcholine on acrylamideinduced lesion. Arzneimittel Stroke Conference. San Antonio, EE. UU., febrero de 2010. forschung 1983; 33: 102933. 219. Giralt D, GarcíaBonilla L, Campos M, Sosti V, Rosell A, 237. Shibuya M, Kageyama N, Taniguchi T, Hidaka H, Fujiwara Montaner J. Selecting the optimal dose of citicoline treatment M. Effects of CDPcholine on striatal dopamine level and in animal models of focal cerebral ischemia through a meta behavior in rats. Jpn J Pharmacol 1981; 31: 4752. analysis. In XIX European Stroke Conference. Barcelona, 238. Stanzani S. Morphological effects of cytidindiphosphate España, 2528 de mayo de 2010. choline on rats with lesions of the substantia nigra: study 220. Drago F, Valerio C, D’Agata V, Spadaro F, Astuto C, Lauria N, using horse radish peroxidase method. Boll Soc It Biol Sper et al. Razionale farmacologico dell’impiego della CDPcolina 1980; 57: 18304. nelle cerebrovasculo patie croniche. Ann Ital Med Int 1989; 239. Porceddu ML, Concas A. Partial protection by CDPcholine 4: 2617. against kainic acidinduced lesion in the rat caudate nucleus. 221. Qureshi I, Endres JR. Citicoline: a novel therapeutic agent with Farmaco Sci 1985; 40: 61722. neuroprotective, neuromodulatory, and neuro regenerative 240. Jiang XY, Jia XJ, Lu WT, Zhao HG, Wang ZC, Gong SL. properties. Nat Med J 2010; 2: 1125. Neuroprotective effects of citicoline on 6hydroxydopamine 222. Saver JL. Target brain: neuroprotection and neurorestoration treated mesencephalic dopaminergic neurons in primary in ischemic stroke. Rev Neurol Dis 2010; 7 (Suppl 1): S1421. culture. Journal of Jilin University (Medicine Edition) 2006; 223. Jambou R, ElAssaad F, Combes V, Grau GE. Citicoline 32: 2247. (CDPcholine): what role in the treatment of complications of 241. Jia XJ, Gong SL, Jiang XY, Qu YQ, WolfDieter R. infectious diseases. Int J Biochem Cell Biol 2009; 41: 146770. Neuroprotective effect of citicoline on dopaminergic neuron 224. Martinet M, Fonlupt P, Pacheco H. Effects of cytidine5’ injury induced by MPP+ in mouse mesencephalic dissociated diphosphocholine on norepinephrine, dopamine and serotonin culture. Journal of Jilin University (Medicine Edition) 2008; synthesis in various regions of the rat brain. Arch Int 34: 536. Pharmacodyn Ther 1979; 239: 5261. 242. Radad K, Gille G, Xiaojing J, Durany N, Rausch WD. CDP 225. Martinet M, Fonlupt P, Pacheco H. Interaction of CDPcholine choline reduces dopaminergic cell loss induced by MPP(+) with synap tosomal transport of biogenic amines and their and glutamate in primary mesencephalic cell culture. Int J precursors in vitro and in vivo in the rat corpus striatum. Neurosci 2007; 117: 9858. Experientia 1978; 34: 11979. 243. Miwa S, Taniguchi T, Fujiwara M, Kurahashi K, Fujiwara M. 226. Martinet M, Fonlupt P, Pacheco H. Activation of Pharmacologi cal studies on CDPcholine with special soluble striatal tyrosine hydroxylase in the rat brain after reference to effects on striatal dopami nergic mechanisms. CDPcholine administration. Biochem Pharmacol 1981; In Zappia V, Kennedy EP, Nilsson BI, Galletti P, eds. Novel 30: 53941. biochemical, pharmacological and clinical aspects of 227. Saligaut C, Daoust M, Moore N, Chretien P, Boismare F. cytidinediphospho choline. Amsterdam: Elsevier Science Capture de dopamine striatale chez le rat: effets d’une Publishing; 1985. p. 17994. hypoxie hypobare aigüe et/ou d’un traitement oral par la 244. Giménez R, Raïch J, Aguilar J. Changes in brain striatum cytidine diphosphocholine. Circ Metab Cerv 1984; 2: 3342. dopamine and acethylcholine receptors induced by chronic 228. Saligaut C, Daoust M, Chadelaud M, Moore N, Chretien P, CDPcholine treatment in aging mice. Br J Pharmacol 1991; Boismare F. Oxotremorineinduced cholinergic syndrome: 104: 5758. modifications by levodopa and/or oral cytidine diphospho 245. Petkov VD, Popova JS. Effects of the nootropic agents choline. Methods Find Exp Clin Pharmacol 1985; 7: 58. adafenoxate, meclofeno xa te and the acetylcholine precursor 229. Saligaut C, Daoust M, Moore N, Boismare F. Effects of hypoxia citicholine on the brain muscarinic receptors (experiments and cytidine (5’) diphosphocholine on the concentration on rats). Acta Physiol Pharmacol Bulg 1987; 13: 310. of dopamine, norepinephrine and metabolites in rat 246. Petkov VD, Stancheva SL, Tocuschieva L, Petkov VV. Changes hypothalamus and striatum. Arch Int Pharmacodyn Ther in brain biogenic monoamines induced by the nootropic 1987; 285: 2533. drugs adafenoxate and meclofenoxate and by citicholine 230. Saligaut C, Daoust M, Moore N, Boismare F. Circling (experiments on rats). Gen Pharmacol 1990; 21: 715. behaviour in rats with unilateral lesions of the nigrostriatum 247. Rejdak R, Toczolowski J, Solski J, Duma D, Grieb P. Citicoline induced by 6hydroxydopamine: changes induced by oral treatment increases retinal dopamine content in rabbits. administration of cytidine5’diphosphocholine. Neuro Ophthalmic Res 2002; 34: 1469. pharmaco logy 1987; 26: 131519. 248. López GonzálezCoviella I, Agut J, Wurtman RJ. Effect of 231. Cansev M, Ilcol YO, Yilmaz MS, Hamurtekin E, Ulus IH. cytidine(5’)diphosphocholi ne (CDPcholine) on the total Peripheral administration of CDPcholine, phosphocholine urinary excretion of 3methoxy4hydroxyphenylglycol (MHPG) or choline increases plasma adrenaline and noradrenaline by rats and humans. J Neural Transm 1986; 66: 12934. concentrations. Auton Autacoid Pharmacol 2008; 28: 4158. 249. Agut J, Watkins C, Maher T, Ortiz JA, Wurtman RJ. Oral 232. Agut J, Coviella I, Wurtman RJ. Cytidine(5’)diphosphocholine CDPcholine administration to rats increases glutamate and enhances the ability of haloperidol to increase dopamine decreases GABA cortical brain levels. In 27th Annual Meeting metabolites in the striatum of the rat and to diminish stereotyped of the Society of Neuroscience. New Orleans, EE. UU., behavior induced by apomorphine. Neurophar macology 2530 de octubre de 1997. 1984; 23: 14036. 250. Cavun S, Savci V, Ulus IH. Centrally injected CDPcholine 233. Agut J, Font E, Saladrich JM, Sacristán A, Ortiz JA. Acción increases plasma vasopressin levels by central cholinergic de la CDPcolina sobre los niveles de los ácidos homovanílico activation. Fundam Clin Pharmacol 2004; 18: 717. S54 www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62
Citicolina: revisión farmacológica y clínica, actualización 2010 251. Cavun S, Savci V. CDPcholine increases plasma ACTH induced antinociception in acute pain models in rats. and potentiates the stimulated release of GH, TSH and LH: Neurosci Lett 2007; 420: 11621. the cholinergic involvement. Fundam Clin Pharmacol 2004; 267. Kamei J, Ohsawa M, Miyata S, Endo K, Hayakawa H. 18: 51323. Effects of cytidine 5’diphosphocholine (CDPcholine) on 252. Savci V, Cavun S, Goktalay G, Ulus IH. Cardiovascular the thermal nociceptive threshold in streptozotocininduced effects of intracerebroventricularly injected CDPcholine in diabetic mice. Eur J Pharmacol 2008; 598: 326. normotensive and hypotensive animals: the involvement of 268. Drago F, Mauceri F, Nardo L, Valerio C, Genazzani AA, Grassi cholinergic system. Naunyn Schmiedebergs Arch Pharmacol M. Effects of cytidinediphosphocholine on acetylcholine 2002; 365: 38898. mediated behaviors in the rat. Brain Res Bull 1993; 31: 4859. 253. Savci V, Goktalay G, Cansev M, Cavun S, Yilmaz MS, Ulus IH. 269. Petkov VD, Mosharrof AH, Petkov VV. Comparative studies Intravenously injected CDPcholine increases blood pressure on the effects of nootropic drugs adafenoxate, meclofenoxate and reverses hypotension in haemorrhagic shock: effect is and piracetamn and of citicholine on scopolamineimpaired mediated by central cholinergic activation. Eur J Pharmacol memory, exploratory behavior and physical capabilities 2003; 468: 12939. (experiments on rats and mice). Acta Physiol Pharmacol Bulg 254. Yilmaz MS, Yalcin M, Savci V. Cytidine 5’diphosphocholine 1988; 14: 313. restores blood flow of superior mesenteric and renal arteries 270. Mosharrof AH, Petkov VD. Effects of citicholine and of and prolongs survival time in haemorrhaged anaesthetized the combination citicholine + piracetam on the memory rats. Clin Exp Pharmacol Physiol 2006; 33: 41520. (experiments on mice). Acta Physiol Pharmacol Bulg 1990; 255. Jochem J, Savci V, Filiz N, RybusKalinowska B, Fogel WA, 16: 2531. Yalcin M. Involvement of the histaminergic system in 271. Petkov VD, Kehayov RA, Mosharrof AH, Petkov VV, Getova cytidine 5’diphosphocholineinduced reversal of critical D, Lazarova MB, et al. Effects of cytidine diphosphate choline heamorrhagic hypotension in rats. J Physiol Pharmacol on rats with memory deficits. Arzneimittelforschung 1993; 2010; 61: 3743. 43: 8228. 256. Cansev M, Yilmaz MS, Ilcol YO, Hamurtekin E, Ulus IH. 272. Álvarez XA, Vecino B, Perea JE, Daniele D, Cacabelos R. Cardiovascular effects of CDPcholine and its metabolites: Citicoline antagonizes bromazepaminduced amnesia in rats. Involvement of peripheral autonomic nervous system. Human Psychopharmacol 1997; 12: 54756. Eur J Pharmacol 2007; 577: 12942. 273. Bruhwyler J, Liégeois JF, Géczy J. Facilitatory effects of 257. Yilmaz MS, Coskun C, Yalcin M, Savci V. CDPcholine chronically administered citicoline on learning and memory prevents cardiac arrhythmias and lethality induced by processes in the dog. Prog Neuropsychopharmacol Biol shortterm myocardial ischemiareperfusion injury in Psychiatry 1998; 22: 11528. the rat: involvement of central muscarinic cholinergic 274. Teather LA, Wurtman RJ. Dietary cytidine (5’)diphospho mechanisms. Naunyn Schmiedebergs Arch Pharmacol 2008; choline supplementation protects against development of 378: 293301. memory deficits in aging rats. Prog Neuropsychopharmacol 258. IsbilBuyukcoskun N, Ilcol YO, Cansev M, Hamurtekin E, Biol Psychiatry 2003; 27: 7117. Ozluk K, Ulus IH. Central choline suppresses plasma renin 275. Teather LA, Wurtman RJ. Dietary CDPcholine supplementation response to graded haemorrhage in rats. Clin Exp Pharmacol prevents memory impairment caused by impoverished Physiol 2008; 35: 102331. environmental conditions in rats. Learn Mem 2005; 12: 3943. 259. Ilcol YO, Cansev M, Yilmaz MS, Hamurtekin E, Ulus IH. 276. De Bruin NM, Kiliaan AJ, De Wilde MC, Broersen LM. Intraperitoneal administration of CDPcholine and its Combined uridine and choline administration improves cholinergic and pyrimidinergic metabolites induce hyper cognitive deficits in spontaneously hypertensive rats. glycemia in rats: involvement of the sympathoadrenal system. Neurobiol Learn Mem 2003; 80: 6379. Arch Physiol Biochem 2007; 113: 186201. 277. De Medio GE, Trovarelli G, Piccinin GL, Porcellati G. The 260. Ilcol YO, Cansev M, Yilmaz MS, Hamurtekin E, Ulus IH. effect of cytidinediphosphate choline (CDPcholine) on brain Peripheral administration of CDPcholine and its cholinergic lipid changes during aging. J Neurosci Res 1984; 11: 4958. metabolites increases serum insulin: muscarinic and 278. López GonzálezCoviella I, Agut J, Ortiz JA, Wurtman RJ. nicotinic acetylcholine receptors are both involved in Effects of orally administered cytidine 5’diphosphate choline their actions. Neurosci Lett 2008; 431: 716. on brain phospholipid content. J Nutr Biochem 1992; 3: 3135. 261. Cansev M, Ilcol YO, Yilmaz MS, Hamurtekin E, Ulus IH. 279. Wang CS, Lee RK. Choline plus cytidine stimulate phospholipid Choline, CDPcholine or phosphocholine increases plasma production, and the expression and secretion of amyloid glucagon in rats: involvement of the peripheral autonomic precursor protein in rat PC12 cells. Neurosci Lett 2000; nervous system. Eur J Pharmacol 2008; 589: 31522. 283: 258. 262. Ilcol YO, Yilmaz Z, Cansev M, Ulus IH. Choline or CDP 280. Plataras C, Angelogianni P, Tsakiris S. Effect of CDPcholine + choline alters serum lipid responses to endotoxin in dogs on hippocampal acetylcholinesterase and Na + ,K ATPase in and rats: involvement of the peripheral nicotinic acetylcholine adult and aged rats. Z Naturforsch C 2003; 58: 27781. receptors. Shock 2009; 32: 28694. 281. Giménez R, Soler S, Aguilar J. Cytidine diphosphate 263. Yilmaz Z, Ozarda Y, Cansev M, Eralp O, Kocaturk M, Ulus IH. choline administration activates brain cytidine triphosphate: Choline or CDPcholine attenuates coagulation abnormalities phosphocholine cytidyltransferase in aged rats. Neurosci Lett and prevents the development of acute disseminated 1999; 273: 1636. intravascular coagulation in dogs during endotoxemia. 282. Giménez R, Aguilar J. Effects of CDPcholine administration Blood Coagul Fibrinolysis 2010; 21: 33948. on brain striatum platelet activating factor in aging rats. 264. Hamurtekin E, Sibel Gurun M. The antinociceptive effects Eur J Pharmacol 1998; 344: 14952. of centrally administered CDPcholine on acute pain models 283. Giménez R, Aguilar J. Cytidine (5’) diphosphocholineinduced in rats: the involvement of cholinergic system. Brain Res decrease in cerebral platelet activating factor is due to 2006; 1117: 92100. inactivation of its synthesizing enzyme cholinephospho 265. Gurun MS, Parker R, Eisenach JC, Vincler M. The effect transferase in aged rats. Neursoci Lett 2001; 299: 20912. of peripherally administered CDPcholine in an acute 284. Giménez R, Aguilar J. Effects of cytidine 5’diphosphocholine inflammatory pain model: the role of alpha7 nicotinic on plasma homocysteine levels in rat. Comp Biochem Physiol acetylcholine receptor. Anesth Analg 2009; 108: 16807. B Biochem Mol Biol 2003; 134: 2716. 266. Hamurtekin E, Bagdas D, Gurun MS. Possible involvement 285. Giuffrida Stella AM, Alberghina M, Avola R, Condorelli DF, of supraspinal opioid and GABA receptors in CDPcholine Ragusa N, Turpeenoja L, et al. Effetto della somministrazione www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62 S55
J.J. Secades cronica di CDPcolina sul metabolismo degli acidi nucleici e Citicoline is not protective in experimental models of delle proteine in diverse aree cerebrali durante Huntington’s disease. Neurobiol Aging 2007; 28: 19446. l’invecchiamento. G Gerontol 1988; 36: 33140. 302. Valdayo M. Tratamiento de las toxicomanías con citidín 286. Avola R, Villa R, Condorelli DF, Magri G, Ingrao F, Turpeenoja difosfato de colina. Phronesis 1983; 5: 3136. L, et al. Agedependent changes on nucleic acid and protein 303. Tornos ME, Sacristán A, Ortiz JA. Effect of oral CDPcholine metabolism in different brain regions: effect of CDPcholine on experimen tal withdrawal syndrome. Arzneimittelforschung treatment. In Post Febs Meeting on Regulation of Gene 1983; 33: 101821. Expression in the Nervous Syst, De Vellis J, PérezPolo JR, 304. Patt S, CervósNavarro J, StoltenburgDidinger G, Schreiner Giuffrida Stella AM, eds. Regulation of gene expression in C. The effects of CDPcholine on newborn rat pups with the nervous system. New York: WileyLiss; 1990. p. 399401. experimental alcohol fetopathy. A Golgi study. Histol 287. Villa RF, Ingrao F, Magri G, Gorini A, Reale S, Costa A, et al. Histopathol 1989; 4: 42934. Effect of CDPcholine treatment on mitochondrial and 305. Petkov VD, Konstantinova ER, Petkov VV, Vaglenova JV. synaptosomal protein composition in different brain regions Learning and memory in rats exposed pre and postnatally during aging. Int J Dev Neurosci 1993; 11: 8393. to alcohol. An attempt at pharmacological control. Methods 288. Deutsch SI, Rosse RB, Schwartz BL, Schooler NR, Gaskins Find Exp Clin Pharmacol 1991; 13: 4350. BL, Long KD, et al. Effects of CDPcholine and the combination 306. Rosario P, Rubio I, De la Morena E. Effects of CDPcholine of CDPcholine and galantamine differ in an animal model administration on in vivo release and biosynthesis of of schizophrenia: development of a selective alpha(7) nicotinic acetylcholine in hippocampus of ethanoltreated rats as acetylcholine receptor agonist strategy. Eur Neuropsycho studied by in vivo brain microdialysis. J Neural Transm 1996; pharmacol 2008; 18: 14751. 103: 467. 289. Petkov VD, Milanov S, Petkov VV. Effects of CDPcholine 307. Rosario P, De la Morena E. CDPcholine reverses opiate and the nootropic drug meclofenoxate on agerelated changes receptorinduced decreases in hippocampal acetylcholine in the blood levels of prolactin and growth hormone. C R Acad release during chronic ethanol consumption and suppresses Bulg Sci 1993; 46: 1379. the withdrawal syndrome. A microdialysis study. In 4th 290. Crespo D, Verduga R, FernándezViadero C, Megías M. Congress of the European Society for Clinical Neuro Structural changes induced by cytidine5’diphosphate pharmacology. Eilat, Israel, 14 de diciembre de 1997. choline (CDPcholine) chronic treatment in neurosecretory 308. Grau T, Romero A, Sacristán A, Ortiz JA. Study on the neurons of the supraoptic nucleus of aged CFWmice. protection of CDPcholine against nicotine intoxication. Mech Ageing Dev 1995; 84: 18393. Arzneimittelforschung 1983; 33: 10256. 291. Crespo D, Megías M, FernándezViadero C, Verduga R. 309. Grau T, Romero A, Sacristán A, Ortiz JA. CDPcholine: Chronic treatment with a precursor of cellular phosphatidyl Acute toxicity study. Arzneimittelforschung 1983; 33: 10334. choline ameliorates morphological and behavioral effects of 310. Matsuda Y, Toda N, Takaori S. Toxicidad aguda, subaguda y aging in the rat hippocampus. Ann N Y Acad Sci 2004; 1019: crónica de la CDPcolina en ratas y conejos. Gendai no Rinsho 413. 1967; 1: 99107. 292. MiguelHidalgo JJ, Álvarez XA, Lagares R, Franco A, 311. Kanabayashi T, Shiota K, Mizuno M, Isaka H, Hoshino H. Fernández L, Cacabelos R. Brain neurotoxic lesions in rats: Toxicological studies on citicoline. Acute and subacute study of the neuroprotective effects of CDPcholine. In XX toxicity study in mice and rats. Aso Yakuri 1980; 20: 10926. CINP Congress. Melbourne, Australia, junio de 1995. 312. Agut J, Font E, Sacristán A, Ortiz JA. Dissimilar effects 293. MiguelHidalgo JJ, Álvarez XA, Lagares R, Franco A, in acute toxicity studies of CDPcholine and choline. Fernández L, Cacabelos R. Protective effects of CDPcholine Arzneimittelforschung 1983; 33: 10168. against neurotoxic lesions in rat brain. In X World Congress 313. Ciaceri G. Toxicological studies on CDPcholine. In Zappia V, of Psychiatry. Madrid, España, 2328 de agosto de 1996. Kennedy EP, Nilsson BI, Galletti P, eds. Novel biochemical, 294. MiguelHidalgo JJ, Álvarez A, Cacabelos R. Plasticity of pharmacological and clinical aspects of cytidinediphospho Congo red staining displayed by subpopulations of neurons choline. Amsterdam: Elsevier Science Publishing; 1985. within the rat central nervous system. Cell Tissue Res 1998; p. 15967. 293: 7586. 314. Schauss AG, SomfaiRelle S, Financsek I, Glavits R, Parent 295. Kenarova B, Vladimirova R, Hadjiivanova C, Petkov VD. SC, Endres JR, et al. Single and repeateddose oral toxicity Immunomodulating effects of cytidine diphosphate choline. studies of citicoline freebase (choline cytidine 5’pyrophosphate) Biomed Lett 1994; 49: 11925. in SpragueDawley rats. Int J Toxicol 2009; 28: 47987. 296. Álvarez XA, Sampedro C, Lozano R, Cacabelos R. Citicoline 315. Romero A, Grau T, Sacristán A, Ortiz JA. Study of subacute protects hippocampal neurons against apoptosis induced by toxicity of CDPcholine after 30 days of oral administration brain betaamyloid deposits plus cerebral hypoperfusion in to rats. Arzneimittelforschung 1983: 33: 10358. rats. Methods Find Exp Clin Pharmacol 1999; 21: 53540. 316. Romero A, Grau T, Sacristán A, Ortiz JA. CDPcholine: 297. Mosharrof AH, Petkov VD, Petkov VV. Effects of meclofenoxate 6month study toxicity in dogs. Arzneimittelforschung 1983: and citicholine on learning and memory in aged rats. Acta 33: 103842. Physiol Pharmacol Bulg 1987; 13: 1724. 317. Agut J, Font E, Sacristán A, Ortiz JA. Bioavailability of methyl 298. Petkov VD, Mosharrof AH, Petkov VV, Kehayov RA. 14 C CDPcholine by oral route. Arzneimittelforschung 1983; Agerelated differences in memory and in the memory 33: 10457. effects of nootropic drugs. Acta Physiol Pharmacol Bulg 1990; 318. López GonzálezCoviella I, Agut J, Von Borstel R, Wurtman 16: 2836. RJ. Metabolism of cytidine (5’)diphosphocholine (CDP 299. Rema V, Bali KK, Ramachandra R, Chugh M, Darokhan Z, choline) following oral and intravenous administration Chaudhary R. Cytidine5diphosphocholine supplement in to the human and the rat. Neurochem Int 1987; 11: 2937. early life induces stable increase in dendritic complexity of 319. López GonzálezCoviella I, Agut J, Savci V, Ortiz JA, neurons in the somatosensory cortex of adult rats. Neuroscience Wurtman RJ. Evidence that 5’cytidinediphosphocholine can 2008; 155: 55664. affect brain phospholipid composition by increasing choline 300. Bramanti V, Campisi A, Tomassoni D, Li Volti G, Caccamo D, and cytidine plasma levels. J Neurochem 1995; 65: 88994. Cannavò G, et al. Effect of acetylcholine precursors on 320. Wurtman RJ, Regan M, Ulus I, Yu L. Effect of oral CDP proliferation and differentiation of astroglial cells in primary choline on plasma choline and uridine levels in humans. cultures. Neurochem Res 2008; 33: 26018. Biochem Pharmacol 2000; 60: 98992. 301. Mievis S, Levivier M, Vassart G, Brotchi J, Ledent C, Blum D. 321. Galletti P, De Rosa M, Nappi MA, Pontoni G, Del Piano L, S56 www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62
Citicolina: revisión farmacológica y clínica, actualización 2010 Salluzzo A, et al. Transport and metabolism of double 341. Deleuze R, Huguenard P, Laborit G, Roujas F. Effets de la labelled CDPcholine in mammalian tissues. Biochem CDPcholine sur le rapport lactates/pyruvates dans le LCR Pharmacol 1985; 34: 412130. en cas de souffrance cérébrale grave. C R Thér 1985; 4: 118. 322. De Rosa M, Galletti P, Romeo G, Nappi A, Pontoni G, 342. Ogasiwa M, Takeuchi K, Hara M, Tanaka Y, Okada J. Studies Arrigoni E, et al. Pharmacokinetics and metabolism of on the intrathecal pharmacotherapy. Part I: CDPcholine. doublelabelled CDPcholine. In Zappia V, Kennedy EP, Int J Clin Pharmacol 1975; 12: 32735. Nilsson BI, Galletti P, eds. Novel biochemical, pharmacological 343. Ogasiwa M, Takeuchi K. Intrathecal pharmacotherapy and clinical aspects of cytidinediphosphocholine. in coma. Acta Neurochir (Wien) 1976; 34: 3744. Amsterdam: Elsevier Science Publishing; 1985. p. 13957. 344. De Blas A, MartínezCubells J, Hernando C. Valoración 323. Romero A, Serratosa J, Sacristán A, Ortiz JA. Highresolution de la efectividad de la citicolina en el tratamiento de los autoradiog raphy in mouse brain 24 h after radiolabelled traumatismos craneoencefálicos. Med Clin (Barc) 1986; 87 CDPcholine administration. Arzneimittelforschung 1983; (Supl 1): S414. 3: 10568. 345. Ragguenneau JL, Jarrige B. Enquête nationale sur les suites des 324. Romero A, Serratosa J, Sacristán A, Ortiz JA. Highresolution traumatis mes crâniens graves: analyse des 219 traumatismes autoradiog raphy in mouse brain and cerebellum 10 days traités par CDPcholine. Agressologie 1988; 29: 43943. after radiolabelled CDPcholine administration. Arzneimittel 346. Calatayud V, Calatayud JB, Aso J. Effects of CDPcholine on forschung 1983; 33: 105860. the recovery of patients with head injury. J Neurol Sci 1991; 325. Romero A, Serratosa J, Sacristán A, Ortiz JA. Lowresolution 103 (Suppl): S158. autoradio graphy in rat brain after administering labelled 347. Lozano R. CDPcholine in the treatment of cranioencephalic CDPcholine. Arzneimittelforschung 1983; 33: 10546. traumata. J Neurol Sci 1991; 103 (Suppl): S437. 326. Agut J, Font E, Sacristán A, Ortiz JA. Radioactivity 348. Levin HS. Treatment of postconcussional symptoms incorporation into different cerebral phsopholipids after oral with CDPcholine. J Neurol Sci 1991; 103 (Suppl): S3942. administration of C methyl CDPcholine. Arzneimittel 349. Aniruddha TJ, Pillai S, Devi BI, Sampath S, Chandramouli 14 forschung 1983; 33: 104850. BA. Role of citicoline in the management of mild head injury. 327. Aguilar J, Giménez R, Bachs O, Enrich C, Agut J. Cerebral Indian J Neurotrauma 2009; 6: 4952. subcellular distribution of CDPcholine and/or its metabolites 350. LeónCarrión J, DomínguezRoldán JM, MurilloCabeza F, after oral administration of methyl C CDPcholine. DomínguezMorales MR, MuñozSánchez MA, Forastero P. 14 Arzneimittelforschung 1983; 33: 10513. Advances in the treatment of memory deficits after brain 328. Savci V, Wurtman RJ. Effect of cytidine on membrane injury: the role of citicholine. In 3rd World Congress on phospholipid synthesis in rat striatal slices. J Neurochem Brain Injury. Quebec, Canadá, 1217 de junio de 1999. 1995; 64: 37884. 351. LeónCarrión J, DomínguezRoldán JM, MurilloCabeza F, 329. Knapp S, Wurtman RJ. Enhancement of free fatty acid DomínguezMorales MR, MuñozSánchez MA. Normalization incorporation into phospholi pids by choline plus cytidine. of memoryrelated cerebral blood flow in severe traumatic Brain Res 1999; 822: 529. brain injury patients and improvements of memory induced 330. Dinsdale JR, Griffiths GK, Rowlands C, Castelló J, Ortiz JA, by citicholine (CDPcholine): the role of a procognitive 14 Maddock J, et al. Pharmacokinetics of C CDPcholine. drug. In International Conference on Recent Advances in Arzneimittelforschung 1983; 33: 106670. Neurotraumatology 1999. Taipei, 2023 de noviembre de 1999. 331. Moriyama M, Tsukumo T, Nakagawa Y. Effects of CDP 352. LeónCarrión J, DomínguezRoldán JM, MurilloCabeza F, choline on head injury. Gendai no Rinsho 1967; 1: 11420. DomínguezMorales MR, MuñozSánchez MA. The role of 332. Ayuso JL, Saiz J. Efecto protector del citidín5difosfato citicholine in neuropsychological training after traumatic de colina sobre el defecto mnésico postelectrochoque. brain injury. Neurorehabilitation 2000; 14: 3340. Munchener Medizinische Wochenschrift (ed. española) 353. Spiers PA, Hochanadel G. Citicoline for traumatic brain 1977; 119: 539. injury: report of two cases, including my own. J Int Neuro 333. De la Herrán J, Cortina C, Salazar J, Fernández F. Utilización psychol Soc 1999; 5: 2604. del citidín difosfato de colina en lesiones encefálicas graves. 354. Chinnock P, Pokkunuri V. CDPcholine for acute traumatic Actas Luso Esp Neurol Psiquiatr Cienc Afines 1978; 6: 312. brain injury. Cochrane Database Syst Rev 2005; 3: CD005402. 334. Carcasonne M, LeTourneau JN. Étude en double insu du 355. Zafonte R, Friedewald WT, Lee SM, Levin B, DíazArrastia R, Réxort en neurotrau matologie infantile. Vie Médicale 1979; Ansel B, et al. The citicoline brain injury treatment (COBRIT) 12: 1007. trial: design and methods. J Neurotrauma 2009; 26: 220716. 335. Espagno J, Trémoulet M, Gigaud M, Espagno C. Étude de 356. Brouns R, De Deyn PP. The complexity of neurobiological l’action de la CDPcholine dans les troubles de la vigilance processes in acute ischemic stroke. Clin Neurol Neurosurg posttraumatique. Vie Médicale 1979; 3: 1956. 2009; 111: 48395. 336. Richer E, Cohadon F. Essai thérapeutique d’un précurseur 357. Rogalewski A, Schneider A, Ringelstein EB, Schabitz WR. des phospholipides sur le traitement des comas traumatiques. Toward a multimodal neuroprotective treatment of stroke. In Symposium International: Souffrance Cérébrale et Stroke 2006; 37: 112936. Précurseurs des Phospholipides. París, Francia, 18 de enero 358. Minnerup J, Schäbitz WR. Multifunctional actions of approved de 1980. and candidate stroke drugs. Neurotherapeutics 2009; 6: 4352. 337. Lecuire J, Duplay J. Sperimentazione in doppio cieco della 359. Zaleska MM, Mercado ML, Chávez J, Feuerstein GZ, Pangalos citicolina versus meclofenossato in pazienti colpiti da trauma MN, Wood A. The development of stroke therapeutics: cranico. G Ital Ric Clin Ter 1982; 3: 515. promising mechanisms and translational challenges. 338. Lecuire J, Duplay J. Sperimentazione della citicolina in un Neuropharmacology 2009; 56: 32941. campione di 154 traumatizzati cranici. G Ital Ric Clin Ter 360. Chavez JC, Zaleska MM, Wang X, Wood A, Hurko O, 1982; 3: 617. Pangalos MN, et al. Multimodal magnetic resonance imaging 339. Lecuire J. Traumatismes crâniens: étude comparative piracetam for assessing evolution of ischemic penumbra: a key translational CDPcholine. C R Ther Pharmacol Clin 1985; 3: 37. medicine strategy to manage the risk of developing novel 340. Cohadon F, Richer E. CDPcholine in severe traumatic coma: therapies for acute ischemic stroke. J Cereb Blood Flow Metab a double blind study. In Zappia V, Kennedy EP, Nilsson BI, 2009; 29: 2179. Galletti P, eds. Novel biochemical, pharmacological and 361. Ducruet AF, Grobelny BT, Zacharia BE, Hickman ZL, Yeh ML, clinical aspects of cytidinediphosphocholine. Amsterdam: Connolly ES. Pharmacotherapy of cerebral ischemia. Expert Elsevier Science Publishing; 1985. p. 299303. Opin Pharmacother 2009; 10: 1895906. www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62 S57
J.J. Secades 362. Tuttolomondo A, Di Sciacca R, Di Raimondo D, Arnao V, 381. Clark WM, Wechsler LR, Sabounjian LA, Schwiderski UE. Renda C, Pinto A, et al. Neuron protection as a therapeutic A phase III randomized efficacy trial of 2000 mg citicoline target in acute ischemic stroke. Curr Top Med Chem 2009; in acute ischemic stroke patients. Neurology 2001; 57: 1595602. 9: 131734. 382. Tilley BC, Marler J, Geller NL, Lu M, Legler J, Brott T, et al. 363. Matsuoka K, Uozumi T, Kano M, Yoshikawa I, Karita M, Use of a global test for multiple outcomes in stroke trials Toda T. Clinical study of the effect of cytidine diphsophate with application to the National Institute of Neurological choline on sequelas of cerebral circulation disorders. Gendai Disorders and Stroke tPA Stroke Trial. Stroke 1996; 27: no Rinsho 1967; 1: 1849. 213642. 364. Miyazaki M. Effects of CDPcholine on sequelas of cerebral 383. Warach S, Benfield A, Schlaug G, Siewert B, Edelman RR. apoplexy. Gendai no Rinsho 1967; 1: 16971. Reduction of lesion volume in human stroke by citicoline 365. Hazama T, Hasegawa T, Ueda S, Sakuma A. Evaluation of the detected by diffusion weighted magnetic resonance imaging: effect of CDPcholine on poststroke hemiplegia employing a pilot study. Ann Neurol 1996; 40: 5278. a doubleblind controlled trial: assessed by a new rating scale 384. Warach S, Pettigrew LC, Dashe JF, Pullicino P, Lefkowitz DM, for recovery in hemiplegia. Int J Neurosci 1980; 11: 21125. Sabounjian L, et al. Effect of citicoline on ischemic lesions as 366. Goas JY, Bastard J, Missoune A. Bilan à 90 jours du traitement measured by diffusionweighted magnetic resonance imaging. des accidents vasculaires cérébraux par la CDPcholine, à Ann Neurol 2000; 48: 71322. propos d’un essai en double insu. In Sympo sium International: 385. Warach SJ, Sabounjian LA. ECCO 2000 study of citicoline Souffrance Cérébrale et Précurseurs des Phospholipides. for treatment of acute ischemic stroke: effects on infarct París, Francia, 18 de enero de 1980. volumes measured by MRI. In 25th International Stroke 367. Boudouresques P, Alonzo B, Michel B. Conduite thérapeutique Conference. New Orleans, EE. UU., 1012 de febrero de 2000. devant un accident vasculaire cérébral: place de la CDP 386. MartínezVila E, Sieira PI. Current status and perspectives of choline. In Sympo sium International: Souffrance Cérébrale neuroprotection in ischemic stroke treatment. Cerebrovasc et Précurseurs des Phospholipides. París, Francia, 18 de Dis 2001; 11 (Suppl 1): S6070. enero de 1980. 387. Dávalos A. Citicolina en el tratamiento del ictus isquémico 368. Corso EA, Arena M, Ventimiglia A, Bizzarro G, Campo G, agudo. Metaanálisis de los estudios clínicos y neuroimagen Rodolico F. La CDPcolina nelle vasculopatie cerebrali: con citicolina en el ictus. In Simposio Satélite, IX Curso en valutazioni cliniche e di semiologia strumentale. Clin Ter Español de la Academia Americana de Neurología. Miami, 1982; 102: 37986. Estados Unidos, 2000. 369. Tazaki Y, Sakai F, Otomo E, Kutsuzawa T, Kameyama M, 388. Stewart LA, Clarke MJ. Practical methodology of meta Omae T, et al. Treatment of acute cerebral infarction with analyses (overviews) using updated individual patient data. a choline precursor in a multicenter doubleblind placebo Cochrane Working Group. Stat Med 1995; 14: 205779. controlled study. Stroke 1988; 19: 2116. 389. Committee for Proprietary Medicinal Products. Points to 370. Schott B, Joyeux O. Valutazione dell’impiego della citicolina consider on application with 1. Metaanalyses 2. One pivotal nella terapia di accidenti ischemici cerebrali. G Ital Ric Clin study. European Agency for the Evaluation of Medicinal Ter 1982; 3: 5660. Products. Londres, 31 de mayo de 2001. 371. Centrone G, Ragno G, Calicchio G. Uso della citicolina ad 390. Dávalos A, Castillo J, ÁlvarezSabín J, Secades JJ, Mercadal J, alti dosaggi nelle affezioni acute cerebrovascolari. Minerva López S, et al. Oral citicoline in acute ischemic stroke: Med 1986; 77: 3713. an individual patient data pooling analysis of clinical trials. 372. Dereux JF, Gallois P. Résultats comparatifs ACTH/citicoline Stroke 2002; 33: 28507. dans la phase initiale des infarctus cérébraux. Gazette Médicale 391. Saver JL, Wilterdink J. Choline precursors in acute and 1987; 94: 825. subacute human stroke: a metaanalysis. Stroke 2002; 33: 353. 373. Franceschi M, Smirne S, Canal N. Treatment of clinical signs 392. Warach S, Harnett K. Dose dependent reduction in infarct and EEG patterns in patients with ‘organic brain syndrome’. growth with citicoline treatment: evidence of neuroprotection Effects of citidindiphospho choline, citicholine. Clin Trials J in human stroke? Stroke 2002; 33: 354. 1982; 19: 7484. 393. Casado A, Secades JJ, Ibarz R, Herdman M, Brosa M. Cost 374. Guillén F, Buendía C, Herrera JA. CDPcholine in the effectiveness of citicoline versus conventional treatment in treatment of acute ischaemic stroke. In 5th Meeting of the acute ischemic stroke. Expert Rev Pharmacoecon Outcomes European Neurological Society. Munich, Alemania, 1721 Res 2008; 8: 1517. de junio de 1995. 394. Sobrino T, Arias S, RodríguezOsorio X, Brea D, Rodríguez 375. Bruhwyler J, Van Dorpe J, Géczy J. Multicentric openlabel González R, Ramos P, et al. CDPcholine treatment improves study of the efficacy and tolerability of citicoline in the treatment functional recovery by an increment of circulating endothelial of acute cerebral infarction. Curr Ther Res 1997; 58: 30916. progenitor cells in human acute ischemic stroke. J Neurochem 376. Fridman EA, Ottaviano F, Fiol M, Javelier A, Perea JE, Ameriso 2007; 101(Suppl 1): S43. SF. Neuroprotección en el ictus isquémico agudo. Factibilidad 395. Cho HJ, Kim YJ. Efficacy and safety of oral citicoline in acute de un protocolo terapéutico. Rev Neurol 2001; 32: 81821. ischemic stroke: drug surveillance study in 4191 cases. 377. Álvarez E, González M. Efectividad y tolerabilidad de la Methods Find Exp Clin Pharmacol 2009; 31: 1716. citicolina en el ictus isquémico agudo, estudio aleatorizado, 396. Secades JJ, ÁlvarezSabín J, Rubio F, Lozano R, Dávalos A, doble ciego comparado con placebo. Archivos Venezolanos Castillo J. Citicoline in intracerebral haemorrhage, a double de Farmacología y Terapéutica 2007; 26: 12730. blind, randomized, placebocontrolled, multicentre pilot 378. LeónJiménez C, Chiquete E, Cantú C, MiramontesSaldaña study. Cerebrovasc Dis 2006; 21: 3805. MJ, AndradeRamos MA, RuizSandoval JL. Citicoline for 397. Eribal MR, Chua RH. Role of intravenous citicoline for acute ischemic stroke in Mexican hospitals: a retrospective supratentorial hemorrhage. In International Stroke Conference. postmarketing analysis. Methods Find Exp Clin Pharmacol San Francisco, EE. UU., 2007. 2010; 32: 32530. 398. Iranmanesh F, Vakilian A. Efficiency of citicoline in increasing 379. Clark WM, Warach SJ, Pettigrew LC, Gammans RE, Sabounjian muscular strength of patients with nontraumatic cerebral LA. A randomized doseresponse trial of citicoline in acute hemorrhage: a doubleblind randomized clinical trial. J Stroke ischemic stroke patients. Neurology 1997; 49: 6718. Cerebrovasc Dis 2008; 17: 1535. 380. Clark W, Williams BJ, Selzer KA, Zweifler RM, Sabounjian 399. Secades JJ. Citicoline in the treatment of intracerebral LA, Gammans RE. A randomized efficacy trial of citicoline hemorrhage. In 4th Western China International Neuroscience in patients with acute ischemic stroke. Stroke 1999; 30: 25927. Forum. Tengchong, China, agosto de 2010. S58 www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62
Citicolina: revisión farmacológica y clínica, actualización 2010 400. Saver JL. Citicoline: update on a promising and widely available an in vivo phosphorus magnetic resonance spectroscopy agent for neuroprotection and neurorepair. Rev Neurol Dis study. Psychopharmacology (Berl) 2002; 161: 24854. 2008; 5: 16777. 422. Silveri MM, Dikan J, Ross AJ, Jensen JE, Kamiya T, Kawada 401. Ortega G, Jacas C, Quintana M, Ribó M, Santamarina E, Y, et al. Citicoline enhances frontal lobe bioenergetics as Maisterra O, et al. Citicoline treatment prevents neurocognitive measured by phosphorus magnetic resonance spectroscopy. decline after a first ischemic stroke. In XIX European Stroke NMR Biomed 2008; 21: 106675. Conference. Barcelona, España, 2528 de mayo de 2010. 423. Renshaw PF, Babb SM, YurgelunTodd DA, Wald LL, 402. Ovbiagele B, Kidwell CS, Starkman S, Saver JL. Potential Villafuerte RA, Cohen BM. Chronic citicholine (CDPcholine) role of neuroprotective agents in the treatment of patients administration alters brain phospholipid metabolites and with acute ischemic stroke. Curr Treat Options Neurol improves cognitive performance in healthy, older adults. 2003; 5: 36775. In 37th ACNP Annual Meeting. San Juan, Puerto Rico, 403. Labiche LA, Grotta JC. Clinical trials for cytoprotection 1418 de diciembre de 1998. in stroke. NeuroRx 2004; 1: 4670. 424. Spiers PA, Myers D, Hochanadel GS, Lieberman HR, 404. Alonso de LeciñanaCases M, Pérez R, DíezTejedor E. Wurtman RJ. Citicoline improves verbal memory in aging. Recomendaciones para el tratamiento y prevención del Arch Neurol 1996; 53: 4418. ictus, 2004. Rev Neurol 2004; 39: 46586. 425. Álvarez XA, Laredo M, Corzo D, FernándezNovoa L, 405. Muñoz Collazos M. Avances en la terapéutica del ACV. Mouzo R, Perea JE, et al. Citicoline improves memory Revista de la Facultad de Ciencias de la Salud de la performance in elderly subjects. Methods Find Exp Clin Universidad del Cauca 2008; 6. Pharmacol 1997; 19: 20110. 406. Davis S, Lees K, Donnan G. Treating the acute stroke patient 426. Sánchez S, García ME, Carrizalez Y, Chaves L, Rodríguez U, as an emergency: current practices and future opportunities. Cárdenas, J, et al. Efectividad y tolerabilidad de la citicolina Int J Clin Pract 2006; 60: 399407. (Somazina) en el tratamiento de pacientes con deterioro 407. Segura T, Calleja S, Jordan J. Recommendations and treatment cognitivo tipo demencia. Archivos Venezolanos de strategies for the management of acute ischemic stroke. Farmacología y Terapéutica 2006; 25: 1013. Expert Opin Pharmacother 2008; 9: 107185. 427. Bettini R, Gorini M. I tempi di reazione in corso di trattamento 408. Jeyaseelan K, Lim KY, Armugam A. Neuroprotectants in con citicolina. Clin Ter 2002; 153: 24750. stroke therapy. Expert Opin Pharmacother 2008; 9: 887900. 428. Madariaga LM, Espina JM, Pascual A, Ortiz LG, Castro JM. 409. Gupta SK, Gupta A, Gondhotra D, Gupta A, Gupta S. Role Estudio doble ciego sobre un grupo de enfermas seniles tratadas of citicoline is ischaemic stroke. JK Science 2008; 10: 1602. con CDPcolina. Rev Psiquiatr Psicol Med 1978; 13: 33142. 410. Schäbitz WR. CDPcholin zur behandlung des schlaganfalls. 429. Fassio B, Fassio M, Pavesi G, Piantato E. La citicolina Psychopharmakotherapie 2009; 16: 1015. in psicogeriatria. Clin Europ 1982; 21: 63546. 411. Clark WM. Efficacy of citicoline as an acute stroke treatment. 430. Lingetti M, Ciarimboli M, Rumiano C, Lingetti E, De Rosa Expert Opin Pharmacother 2009; 10: 83946. A, Resciniti C, et al. Cerebropatie involutive senili gravi: 412. Estrategia en Ictus del Sistema Nacional de Salud. Ministerio trattamento con citicolina ad alto dosaggio. Rass Int Clin de Sanidad y Consumo. Gobierno de España. 2008. Ter 1982; 62: 70414. 413. Management of patients with stroke or TIA: assessment, 431. StrambaBadiale M, Scillieri E. Attività della citicolina nel investigation, immediate management and secondary decadimento mentale senile. Minerva Med 1983; 74: 81921. prevention. A national clinical guideline. Scottish Intercollegiate 432. Bonavita E, Chioma V, Dall’Oca P, Fini C, Michelini M, Ruggi Guidelines Network. December 2008. MR, et al. Studio in doppio cieco sull’azione della citicolina 414. Dávalos A. Protocol 06PRT/3005: ICTUS study: International nel cervello senile. Minerva Psichiatr 1983; 24: 5362. Citicoline Trial on acUte Stroke (NCT00331890) Oral 433. Lozano R, Fernández MV, Balagué A. Alteraciones neuropsíquicas citicoline in acute ischemic stroke. Lancet Protocol Reviews del anciano: evolución tras la administración de CDPcolina 2007. URL: http://www.thelancet.com/journals/lancet/misc/ (citicolina). Med Clin (Barc) 1986; 87 (Supl 1): S303. protocol/protocolreviews. 434. Palleschi M, Capobianco G. Invecchiamento cerebrale 415. ICTUS Study: International Citicoline Trial on Acute Stroke. patologico. Osservazio ni personali con l’impiego della URL: http://clinicaltrials.gov/ct2/show/NCT00331890?term citicolina. Clin Ter 1988; 125: 1218. =ictus&rank=1. 435. Schergna E, Lupo L. La citicolina nella medicina di base: 416. Bolland K, Whitehead J, Cobo E, Secades JJ. Evaluation of a esperienza clinica multicentrica nell’area VenetoTrentino sequential global test of improved recovery following stroke Alto AdigeFriuli Venezia Giulia. Giornale di Gerontologia as applied to the ICTUS trial of citicoline. Pharm Stat 2008; 1988; 36: 34150. 8: 13649. 436. Suryani LK, Adnjana TA, Jensen GD. Citicoline treatment 417. Wang J, Zhang HY, Tang XC. Cholinergic deficiency involved of memory deficits in elderly people. Int J Geriatr Psychiatry in vascular dementia: possible mechanism and strategy of 1988; 3: 2356. treatment. Acta Pharmacol Sin 2009; 30: 87988. 437. Serra F, Diaspri GP, Gasbarrini A, Giancane S, Rimondi A, 418. GarcíaCobos R, FrankGarcía A, GutiérrezFernández M, Tamè MR, et al. Effetto della CDPcolina sul decadimen to DíezTejedor E. Citicoline, use in cognitive decline: vascular mentale senile. Esperienza policentrica su 237 casi. Minerva and degenerative. J Neurol Sci 2010; 299: 18892. Med 1990; 81: 46570. 419. Babb SM, Appelmans KE, Renshaw PF, Wurtman RJ, Cohen 438. Lingetti M, Carimboli M, Porfido FA, De Paola P, Barlattani MP. BM. Differential effect of CDPcholine on brain cytosolic Effetti della CDPcolina su alcuni parametri neuropsicologici choline levels in younger and older subjects as measured by in pazienti con involuzione cerebrale senile. Riforma Med proton magnetic resonance spectroscopy. Psychopharmacology 1990; 105: 116. 1996; 127: 8894. 439. Di Trapani G, Fioravanti M. La citicolina nell trattamento 420. Wald LL, Babb SM, YurgelunTodd DA, Cohen BM, Renshaw dei disturbi cognitivi e comportamentali del decadimento RF. CDPcholine decreases brain phosphomonoesters in senile patologico. Clin Ter 1991; 137: 40313. normal elderly subjects. In 6th Annual Meeting of the 440. Matsuoka T, Kawanaka M, Nagai K. Effect of cytidine International Society for Magnetic Resonance in Medicine. diphosphate choline on growth hormone and prolactin Sydney, Australia, abril de 1998. secretion in man. Endocrinol Jpn 1978; 25: 557. 421. Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, 441. Ceruso D, D’Andrea Petrelli L, Ciraolo O, Corica F, Petrelli YurgelunTodd DA, et al. Chronic citicoline increases RM. Effect of cytocholine on pituitary function in the elderly. phosphodiesters in the brains of healthy older subjects: Acta Ther 1983; 9: 414. www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62 S59
J.J. Secades 442. Ceda GP, Ceresini G, Magnani D, Marchini L, Valenti G, 460. Tanaka Y, Minematsu K, Hirano T, Hayashida K, Yamaguchi Hoffman AR. Effects of cytidine 5’diphosphocholine T. Effects of CDPcholine on dynamic changes in LCBF and administration on basal and growth hormonereleasing cognitive function in demented subjects. An H OPET study. 15 2 hormoneinduced growth hormone secretion in elderly Rinsho Shinkeigaku 1994; 34: 87781. people. Acta Endocrinol 1991; 124: 51620. 461. Lozano R. Estudio de la evolución del deterioro psicoorgánico 443. Fioravanti M, Buckley AE, Agnoli A, Nappi G, Arrigo A, en el anciano. Tratamiento con CDPcolina. Rev Esp Geriatr Gerstenbrand F. Citicoline in CCVD patients: preliminary Gerontol 1989; 24 (Supl 1): S6572. results of a multicenter study. In Internatio nal Multidisciplinar 462. Corona GI, Santagostino G, Frattini P, Cucchi ML, Zerbi F, Seminar on Cerebral Pathology in Old Age: Neuroradiologi Tosca P, et al. Preliminary data on monoamine metabolite cal and Neurophysiological Correlations. Pavía, Italia, 2728 levels in cerebrospinal fluid and in urine during therapy in de septiembre de 1982. dementia. IRCS Med Sci 1983; 11: 9234. 444. Falchi Delitalia G, Falchi Delitalia N, Casali R, Crescenzi GS, 463. Cacabelos R, Álvarez XA, Franco A, FernándezNovoa L, Attorri L, Lombardi R, et al. Studio a medio termine, in doppio Caamaño J, Del ValleInclán F. Therapeutic effects of CDP cieco versus placebo, con CDPcolina nella insufficenza choline in Alzheimer’s disease and multiinfarct dementia: cerebrale senili. Aspetti psichici, endocrinologici, emoreologici psychometric assessment and immune function. Ann Psychiatr e biochimico ematologici. Gazz Med It 1984; 143: 789810. 1992; 3: 23345. 445. Moglia A, Arrigo A, Bono G, Sinforiani E, Calabro G, Cinanni 464. Caamaño J, Gómez MJ, Franco A, Cacabelos R. Effects of G, et al. Citicoline in patients with chronic cerebrovascular CDPcholine on cognition and cerebral hemodynamics in diseases (CCVD): Quantitative EEG study. Curr Ther Res patients with Alzheimer’s disease. Methods Find Exp Clin 1984; 36: 30913. Pharmacol 1994; 16: 2118. 446. Merchan C, Berchicci R, Cuzzoni G, Pecorini M. CDP 465. FernándezNovoa L, Álvarez XA, FrancoMaside A, Caamaño colina e insufficenza cerebrovascolare nell’anziano. Studio J, Cacabelos R. CDPcholineinduced blood histamine changes clinico di 40 pazienti in corso di trattamento prolungato. in Alzheimer’s disease. Methods Find Exp Clin Pharmacol Minerva Cardioangiol 1985; 33: 1458. 1994; 16: 27984. 447. Agnoli A, Fioravanti M, Lechner H. Efficacy of CDPcholine 466. Cacabelos R, Caamaño J, Gómez MJ, FernándezNovoa L, in chronic cerebral vascular diseases (CCV). In Zappia V, FrancoMaside A, Álvarez XA. Therapeutic effects of CDP Kennedy EP, Nilsson BI, Galletti P, eds. Novel biochemical, choline in Alzheimer’s disease. Cognition, brain mapping, pharmacological and clinical aspects of cytidinediphospho cerebrovascular hemodynamics, and immune factors. Ann choline. Amsterdam: Elsevier Science Publishing; 1985. p. 30515. N Y Acad Sci 1996; 777: 399403. 448. Sinforiani E, Trucco M, Pacchetti C, Gualtieri S. Valutazione 467. Álvarez XA, Mouzo R, Pichel V, Pérez P, Laredo M, Fernández degli effetti della citicolina nella malattia cerebrovascolare Novoa L, et al. Doubleblind placebocontrolled study with cronica. Minerva Med 1986; 77: 517. citicoline in APOE genotyped Alzheimer’s disease patients. 449. Motta L, Fichera G, Tiralosi G, Di Stefano A. La citicolina Effects on cognitive performance, brain bioelectrical activity nel trattamento delle cerebrovasculopatie croniche. Giornale and cerebral perfusion. Methods Find Exp Clin Pharmacol di Gerontologia 1986; 34: 14958. 1999; 21: 63344. 450. Rossi M, Zanardi M. Studio in aperto sull’efficacia clinica 468. Soto A, Ruiz A, Medina C, Alonso A, Viaña JL. An evolutive della citicolina in pazienti affetti da cerebrovasculopatia study of the global impairment in patients diagnosed of senil cronica. Clin Ter 1993; 142: 1414. and presenil pimary degenerati ve dementia of the Alzheimer 451. Fioravanti M. La cerebropatie vascolari croniche: la terapia type (DTA) and undergoing to medical treatment with con CDPcolina. Ann Ital Med Int 1989; 4: 26873. citicoline; calcium antagonist and piracetam. In Beregi E, 452. Raji A, Winkler G. Treatment of cognitive impairment in Gergely IA, Rajczi K, eds. Recent advances in aging science. small vessel stroke and white matter disease with CDPcholine. Bologna: Monduzzi Editore; 1993. p. 7239. In XIX European Stroke Conference. Barcelona, España, 469. Cacabelos R, Álvarez A, FernándezNovoa L, Lombardi VR. 2528 de mayo de 2010. A pharmacogenomic approach to Alzheimer’s disease. Acta 453. Zapadnyuk BV, Kopchak OO. Features drug correction of Neurol Scand Suppl 2000; 176: 129. vascular cognitive disorders in patients with discirculatory 470. Fioravanti M, Yanagi M. Cytidinediphosphocholine encephalopathy and metabolic syndrome. Pro Neuro 2010; (CDPcholine) for cognitive and behavioural disturbances 4: 7782. associated with chronic cerebral disorders in the elderly. 454. Kopchak OO. Efficay of citicoline in the treatment of patients Cochrane Database Syst Rev 2005; 2: CD000269. with vascular cognitive impairment. In 20th Meeting of the 471. Deutsch SI, Schwartz BL, Schooler NR, Rosse RB, Mastropaolo European Neurological Society. Berlín, Alemania, 1923 de J, Gaskins B. First administration of cytidine diphospho choline junio de 2010. and galantamine in schizophrenia: a sustained alpha7 nicotinic 455. Eberhardt R, Dehrr I. Eficacia y tolerancia de CDPcolina agonist strategy. Clin Neuropharmacol 2008; 31: 349. en pacientes geriátricos con insuficiencia cerebral senil. 472. AbadSantos F, NovalbosReina J, GallegoSandín S, García Estudio doble ciego cruzado. Rev Esp Geriatr Gerontol AG. Tratamiento del deterioro cognitivo leve: utilidad de la 1989; 24 (Supl 1): S7381. citicolina. Rev Neurol 2002; 35: 67582. 456. Chandra B. Treatment of multiinfarct dementia with 473. Fioravanti M, Buckley AE. Citicoline (Cognizin) in the citicholine. J Stroke Cerebrovasc Dis 1992; 2: 2323. treatment of cognitive impairment. Clin Interv Aging 2006; 457. Piccoli F, Battistini N, Carbonin P, Dossi BC, Fiori L, La Bella 1: 24751. V, et al. CDPcholine in the treatment of chronic cerebro 474. Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta F. vasculopathies. Arch Gerontol Geriatr 1994; 18: 1618. Cholinergic precursors in the treatment of cognitive impairment 458. Capurso A, Capurso S, Panza F, Solfrizzi V, Mastroianni F, of vascular origin: ineffective approaches or need for Giaquinto S, et al. Efficacy of cytidine diphosphate choline reevaluation? J Neurol Sci 2007; 257: 2649. in patients affected by chronic cerebrovascular disease. 475. Amenta F, Di Tullio MA, Tomassoni D. The cholinergic Clin Drug Investig 1996; 12: 2638. approach for the treatment of vascular dementia: evidence 459. Cohen RA, Browndyke JN, Moser DJ, Paul RH, Gordon N, from preclinical and clinical studies. Clin Exp Hypertens Sweet L. Longterm citicoline (cytidine diphosphate choline) 2002; 24: 697713. use in patients with vascular dementia: neuroimaging and 476. Shimamoto K, Hirano T, Aramaki Y. Therapeutic mechanism neuropsychological outcomes. Cerebrovasc Dis 2003; 16: of cytidine diphosphate choline (CDPcholine) in parkinsonism. 199204. Journal of the Takeda Research Laboratory 1975; 34: 4408. S60 www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62
Citicolina: revisión farmacológica y clínica, actualización 2010 477. Ruggieri S, Zamponi A, Casacchia M, Agnoli A. Effetti with bipolar disorder and cocaine dependence. J Clin Psycho terapeutici della citicolina (citidindifosfocolina) nella pharmacol 2007; 27: 498502. sindrome parkinsoniana. Clin Ter 1976; 78: 51525. 494. Ross BM, Moszczynska A, Peretti FJ, Adams V, Schmunk GA, 478. Agnoli A, Ruggieri S, Denaro A, Bruno G. New strategies in Kalasinsky KS, et al. Decreased activity of brain phospholipid the manage ment of Parkinson’s disease: a biological approach metabolic enzymes in human users of cocaine and using a phospholipid precursor (CDPcholine). Neuro methamphetamine. Drug Alcohol Depend 2002; 67: 739. psychobiology 1982; 8: 28996. 495. Yoon SJ, Lyoo IK, Kim HJ, Kim TS, Sung YH, Kim N, et al. 479. Agnoli A, Ruggieri S, Baldassarre M, Stocchi F, Del Roscio S, Neurochemical alterations in methamphetaminedependent Gallucci M, et al. Current concept in the treatment of Parkinson patients treated with cytidine5’diphosphate choline: disease: use of citicoline. In Yahr MD, ed. Current concepts a longitudinal proton magnetic resonance spectroscopy of Parkinson disease and related disorders. Amsterdam: study. Neuropsychopharmacology 2010; 35: 116573. Excerpta Medica; 1983. p. 12440. 496. Killgore WD, Ross AJ, Kamiya T, Kawada Y, Renshaw PF, 480. Eberhardt R, Gerstenbrand F, Klingler D, Birbamer G, YurgelunTodd DA. Citicoline affects appetite and cortico Ransmayr G. Estudio sobre la eficacia de la combinación de limbic responses to images of highcalorie foods. Int J Eat CDPcolina y levodopa más un inhibidor de la decarboxilasa Disord 2010; 43: 613. en pacientes con enfermedad de Parkinson. Med Clin (Barc) 497. Campos EC, Schiavi C, Benedetti P, Bolzani R, Porciatti V. 1986; 87 (Supl 1): S3440. Effect of citicoline on visual acuity in amblyopia: preliminary 481. Poewe W, Gerstenbrand F. New trends in the therapy of results. Graefes Arch Clin Exp Ophthalmol 1995; 233: 30712. Parkinson’s disease. In Agnoli A, Bertolani G, eds. Atti della 498. Campos EC, Bolzani R, Schiavi C, Baldi A, Porciatti V. VIII Riunione della Lega Italiana per la Lotta Contro il Morbo Cytidin5’diphosphocholi ne enhances the effect of parttime di Parkinson e le Malattie Extrapiramidali. Roma: Publ. D. occlusion in amblyopia. Doc Ophthalmol 1997; 93: 24763. Guanella; 1982. p. 17188. 499. Campos EC. Future directions in the treatment of amblyopia. 482. Eberhardt R, Birbamer G, Gerstenbrand F, Rainer E, Traegner Lancet 1997; 349: 1190. H. Citicoline in the treatment of Parkinson’s disease. Clin Ther 500. Porciatti V, Schiavi C, Benedetti P, Baldi A, Campos EC. 1990; 12: 48995. Cytidine5’diphospho choline improves visual acuity, contrast 483. Birbamer G, Gerstenbrand F, Rainer E, Eberhardt R. CDP sensitivity and visuallyevoked potentials of amblyopic choline in the treatment of Parkinson syndrome. New Trends subjects. Curr Eye Res 1998; 17: 1418. in Clinical Neuropharmacology 1990; 4: 2934. 501. Simons K. Amblyopia characterization, treatment, 484. Loeb C, Albano C, Caraceni T, Caraffa T, Coppi R, Di Perri and prophylaxis. Surv Ophthalmol 2005; 50: 12366. R, et al. CDPcholine in the treatment of Parkinson’s disease: 502. Campos EC, Fresina M. Medical treatment of amblyopia: a multicenter controlled trial. In Zappia V, Kennedy EP, present state and perspectives. Strabismus 2006; 14: 713. Nilsson BI, Galletti P, eds. Novel biochemical, pharmacological 503. Fresina M, Dickmann A, Salerni A, De Gregorio F, Campos and clinical aspects of cytidinediphosphocholine. Amsterdam: EC. Effect of oral CDPcholine on visual function in young Elsevier Science Publishing; 1985. p. 33946. amblyopic patients. Graefes Arch Clin Exp Ophthalmol 2008; 485. Acosta J, Nombela M, Palao A, Pastor M, Recuero J. 246: 14350. Multicentre trial: treatment of Parkinson’s disease with 504. Parisi V, Manni G, Colacino G, Bucci MG. Cytidine5’ CDPcholine (citicholine). In Bartko D, Turcáni P, Stern G, diphosphocholine (citicoline) improves retinal and cortical eds. New trends in clinical neuropharmacology: calcium responses in patients with glaucoma. Ophthalmology 1999; antagonists, acute neurology, headache and movement 106: 112634. disorders. London: John Libbey; 1988. p. 28996. 505. ParisiV. Electrophysiological assessment of glaucomatous 486. Cubells JM, Hernando C. Clinical trial on the use of cytidine visual dysfunction during treatment with cytidine5’ diphosphate choline in Parkinson’s disease. Clin Ther 1988; diphosphocholine (citicoline): a study of 8 years of followup. 10: 66471. Doc Ophthalmol 2005; 110: 91102. 487. MartíMassó JF, Urtasun M. Citicoline in the treatment 506. Virno M, PecoriGiraldi J, Liguori A, De Gregorio F. of Parkinson’s disease. Clin Ther 1991; 13: 23942. The protective effect of citicoline on the progression of the 488. GarcíaMás A, Rossiñol A, Roca M, Lozano R, Rosselló J, perimetric defects in glaucomatous patients (perimetric Llinás J. Efectos de la citicolina en la demencia subcortical study with a 10year followup). Acta Ophthalmol Scand asociada a la enfermedad de Parkinson valorada mediante 2000; 78: 5657. electroencefalografía cuantificada. Clin Ther 1992; 14: 71829. 507. Grieb P, Rejdak R. Pharmacodynamics of citicoline relevant 489. Chinchilla A, LópezIbor JJ, Vega M, Camarero M. CDPcolina to the treatment of glaucoma. J Neurosci Res 2002; 67: 1438. en la evolución de las funciones mentales en el síndrome de 508. Rejdak R, Toczolowski J, Kurkowski J, Kaminski ML, Rejdak K, abstinencia alcohólica. Psiquiatría Biológica 1995; 2: 1715. Stelmasiak Z, et al. Oral citicoline treatment improves visual 490. Renshaw PF, Daniels S, Lundahl LH, Rogers V, Lukas SE. pathway function in glaucoma. Med Sci Monit 2003; 9: PI248. Shortterm treatment with citicoline (CDPcholine) attenuates 509. Parisi V, Coppola G, Centofanti M, Oddone F, Angrisani AM, some measures of craving in cocainedependent subjects: a Ziccardi L, et al. Evidence of the neuroprotective role of preliminary report. Psychopharmacology 1999; 142: 1328. citicoline in glaucoma patients. Prog Brain Res 2008; 173: 54154. 491. Lukas SE, Kouri EM, Rhee C, Madrid A, McNeil J, Renshaw 510. Parisi V, Coppola G, Ziccardi L, Gallinaro G, Falsini B. PF. Citicoline treatment for cocaine abuse: effects of acute Cytidine5’diphosphocholine (Citicoline): a pilot study cocaine challenge on subjective mood and cardiovascular in patients with nonarteritic ischaemic optic neuropathy. responses in adult male and female volunteers. Drug Alcohol Eur J Neurol 2008; 15: 46574. Depend 2001; 63 (Suppl 1): S94. 511. Dinsdale JR, Griffths GK, Castelló J, Maddock J, Ortiz JA, 492. Lukas SE, Kouri EM, Rhee C, Madrid A, Renshaw PF. Effects Aylward M. CDPcholine: Repeated oral dose tolerance of shortterm citicoline treatment on acute cocaine intoxication studies in adult healthy volunteers. Arzneimittelforschung and cardiovascular effects. Psychopharmacology 2001; 157: 1983; 33: 10615. 1637. 512. Lozano R. Efficay and safety of oral CDPcholine. Drug 493. Brown ES, Gorman AR, Hynan LS. A randomized, placebo surveillance study in 2817 cases. Arzneimittelforschung 1983; controlled trial of citicoline addon therapy in outpatients 33: 107380. www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62 S61
J.J. Secades Citicoline: pharmacological and clinical review, 2010 update Summary. This review is based on the previous one published in 2006 –Secades JJ, Lorenzo JL. Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Clin Pharmacol 2006; 28 (Suppl B): S1-56–, incorporating the new references until now, having all the information available to facilitate the access to the información in one document. This review is focused on the main indications of the drug, as acute stroke and its sequelae, including the cognitive impairment, and traumatic brain injury and its sequelae. There are retrieved the most important experimental and clinical data in both indications. Key words. Alcoholism. Alzheimer disease. Amblyopia. Apoptosis. CDP-choline. Cerebral edema. Cerebral ischemia. Citicoline. Cognitive disorder. Drug addiction. Glaucoma. Head injury. Memory. Neuronal membrane. Neuroplasticity. Neuro protection. Neurorepair. Neurotransmission. Parkinson disease. Phosphatidylcholine. Phospholipase. Senile dementia. Stroke. Structural phospholipids. Traumatic brain injury. S62 www.neurologia.com Rev Neurol 2011; 52 (Supl 2): S1-S62
Search
