, Volume 70, Issue 3, pp 287–312 | Cite as

Piracetam and Piracetam-Like Drugs

From Basic Science to Novel Clinical Applications to CNS Disorders
  • Andrei G. Malykh
  • M. Reza SadaieEmail author
Review Article


There is an increasing interest in nootropic drugs for the treatment of CNS disorders. Since the last meta-analysis of the clinical efficacy of piracetam, more information has accumulated. The primary objective of this systematic survey is to evaluate the clinical outcomes as well as the scientific literature relating to the pharmacology, pharmacokinetics/pharmacodynamics, mechanism of action, dosing, toxicology and adverse effects of marketed and investigational drugs. The major focus of the literature search was on articles demonstrating evidence-based clinical investigations during the past 10 years for the following therapeutic categories of CNS disorders: (i) cognition/memory; (ii) epilepsy and seizure; (iii) neurodegenerative diseases; (iv) stroke/ischaemia; and (v) stress and anxiety.

In this article, piracetam-like compounds are divided into three subgroups based on their chemical structures, known efficacy and intended clinical uses. Subgroup 1 drugs include piracetam, oxiracetam, aniracetam, pramiracetam and phenylpiracetam, which have been used in humans and some of which are available as dietary supplements. Of these, oxiracetam and aniracetam are no longer in clinical use. Pramiracetam reportedly improved cognitive deficits associated with traumatic brain injuries. Although piracetam exhibited no long-term benefits for the treatment of mild cognitive impairments, recent studies demonstrated its neuroprotective effect when used during coronary bypass surgery. It was also effective in the treatment of cognitive disorders of cerebrovascular and traumatic origins; however, its overall effect on lowering depression and anxiety was higher than improving memory. As add-on therapy, it appears to benefit individuals with myoclonus epilepsy and tardive dyskinesia. Phenylpiracetam is more potent than piracetam and is used for a wider range of indications. In combination with a vasodilator drug, piracetam appeared to have an additive beneficial effect on various cognitive disabilities. Subgroup 2 drugs include levetiracetam, seletracetam and brivaracetam, which demonstrate antiepileptic activity, although their cognitive effects are unclear. Subgroup 3 includes piracetam derivatives with unknown clinical efficacies, and of these nefiracetam failed to improve cognition in post-stroke patients and rolipram is currently in clinical trials as an antidepressant. The remaining compounds of this subgroup are at various preclinical stages of research.

The modes of action of piracetam and most of its derivatives remain an enigma. Differential effects on subtypes of glutamate receptors, but not the GABAergic actions, have been implicated. Piracetam seems to activate calcium influx into neuronal cells; however, this function is questionable in the light of findings that a persistent calcium inflow may have deleterious impact on neuronal cells. Although subgroup 2 compounds act via binding to another neuronal receptor (synaptic vesicle 2A), some of the subgroup 3 compounds, such as nefiracetam, are similar to those of subgroup 1. Based on calculations of the efficacy rates, our assessments indicate notable improvements in clinical outcomes with some of these agents.


NMDA Receptor Mild Cognitive Impairment Chronic Fatigue Syndrome Levetiracetam Piracetam 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Dr Allan Kalueff who is affiliated with the Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA and Dr Nasi Samiy who is with the Retina Institute of the Carolinas and The Macular Degeneration Center, Rock Hill, SC, USA, for their critical reviewing of the manuscript.

The authors have no financial relationship with and did not receive funds from companies developing and marketing piracetam and related products or their competitors.


  1. 1.
    Giurgea C. The ‘nootropic’ approach to the pharmacology of the integrative activity of the brain. Cond Reflex 1973 Apr–Jun; 8(2): 108–15PubMedGoogle Scholar
  2. 2.
    Piracetam [online]. Available from URL: [Accessed 2010 Jan 22]
  3. 3.
    US National Institutes of Health. [online]. Available from URL: [Accessed 2010 Jan 22]
  4. 4.
    Waegemans T, Wilsher CR, Danniau A, et al. Clinical efficacy of piracetam in cognitive impairment: a meta-analysis. Dement Geriatr Cogn Disord 2002; 13(4): 217–24PubMedCrossRefGoogle Scholar
  5. 5.
    Wheble PC, Sena ES, Macleod MR. A systematic review and meta-analysis of the efficacy of piracetam and piracetam-like compounds in experimental stroke. Cerebrovasc Dis 2008; 25(1-2): 5–11PubMedCrossRefGoogle Scholar
  6. 6.
    Gualtieri F, Manetti D, Romanelli MN, et al. Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs. Curr Pharm Des 2002; 8(2): 125–38PubMedCrossRefGoogle Scholar
  7. 7.
    Information letter from the Institute of Medical-Biological Problems of the Russian Academy of Sciences [in Russian; online]. Available from URL: [Accessed 2010 Jan 22]
  8. 8.
    Nickolson VJ, Wolthuis OL. Effect of the acquisition-enhancing drug piracetam on rat cerebral energy metabolism: comparison with naftidrofuryl and methamphe-tamine. Biochem Pharmacol 1976 Oct 15; 25(20): 2241–4PubMedCrossRefGoogle Scholar
  9. 9.
    Grau M, Montero JL, Balasch J. Effect of Piracetam on electrocorticogram and local cerebral glucose utilization in the rat. Gen Pharmacol 1987; 18(2): 205–11PubMedCrossRefGoogle Scholar
  10. 10.
    Tacconi MT, Wurtman RJ. Piracetam: physiological disposition and mechanism of action. Adv Neurol 1986; 43: 675–85PubMedGoogle Scholar
  11. 11.
    Wischer S, Paulus W, Sommer M, et al. Piracetam affects facilitatory I-wave interaction in the human motor cortex. Clin Neurophysiol 2001 Feb; 112(2): 275–9PubMedCrossRefGoogle Scholar
  12. 12.
    Horvath B, Marton Z, Halmosi R, et al. In vitro antioxidant properties of pentoxifylline, piracetam, and vinpocetine. Clin Neuropharmacol 2002 Jan–Feb; 25(1): 37–42PubMedCrossRefGoogle Scholar
  13. 13.
    Pepeu G, Spignoli G. Nootropic drugs and brain cholinergic mechanisms. Prog Neuropsychopharmacol Biol Psychiatry 1989; 13 Suppl.: S77–8PubMedCrossRefGoogle Scholar
  14. 14.
    Pilch H, Müller WE. Piracetam elevates muscarinic cholinergic receptor density in the frontal cortex of aged but not of young mice. Psychopharmacology (Berl) 1988; 94(1): 74–8CrossRefGoogle Scholar
  15. 15.
    Perucca E, Albrici A, Gatti G, et al. Pharmacokinetics of oxiracetam following intravenous and oral administration in healthy volunteers. Eur J Drug Metab Pharmacokinet 1984Jul–Sep;9(3):267–74PubMedCrossRefGoogle Scholar
  16. 16.
    Chang T, Young RM, Goulet JR, et al. Pharmacokinetics of oral pramiracetam in normal volunteers. J Clin Pharmacol 1985 May–Jun; 25(4): 291–5PubMedGoogle Scholar
  17. 17.
    Auteri A, Blardi P, Celasco G, et al. Pharmacokinetics of pramiracetam in healthy volunteers after oral administration. Int J Clin Pharmacol Res 1992; 12(3): 129–32PubMedGoogle Scholar
  18. 18.
    Endo H, Tajima T, Yamada H, et al. Pharmacokinetic study of aniracetam in elderly patients with cerebrovascular disease. Behav Brain Res 1997 Feb; 83(1–2): 243–4PubMedCrossRefGoogle Scholar
  19. 19.
    Spektor SS, Berlyand AS. Molecular-biological problems of drug design and mechanisms of drug action: experimental pharmacokinetics of carphedon. Pharm Chem J 1996; 30(8): 89–90CrossRefGoogle Scholar
  20. 20.
    Antonova MI, Prokopov AA, Berlyand AS, et al. Experimental pharmacokinetic of Phenotropil in rats. Pharm Chem J 2003; 37: 7–8Google Scholar
  21. 21.
    Sargentini-Maier ML, Rolan P, Connell J, et al. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males. Br J Clin Pharmacol 2007 Jun; 63(6): 680–8PubMedCrossRefGoogle Scholar
  22. 22.
    Rolan P, Sargentini-Maier ML, Pigeolet E, et al. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after multiple increasing oral doses in healthy men. Br J Clin Pharmacol 2008 Jul; 66(1): 71–5PubMedCrossRefGoogle Scholar
  23. 23.
    Bennett B, Matagne A, Michel P, et al. Seletracetam (UCB 44212). Neurotherapeutics 2007 Jan; 4(1): 117–22PubMedCrossRefGoogle Scholar
  24. 24.
    Tai KK, Truong DD. Brivaracetam is superior to levetiracetam in a rat model of post-hypoxic myoclonus. J Neural Transm 2007; 114(12): 1547–51PubMedCrossRefGoogle Scholar
  25. 25.
    Zhao X, Kuryatov A, Lindstrom JM, et al. Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons. Mol Pharmacol 2001 Apr; 59(4): 674–83PubMedGoogle Scholar
  26. 26.
    Fujimaki Y, Sudo K, Hakusui H, et al. Single- and multiple-dose pharmacokinetics of nefiracetam, a new nootropic agent, in healthy volunteers. J Pharm Pharmacol 1992 Sep; 44(9): 750–4PubMedCrossRefGoogle Scholar
  27. 27.
    Iwasaki K, Matsumoto Y, Fujiwara M. Effect of nebracetam on the disruption of spatial cognition in rats. Jpn J Pharmacol 1992 Feb; 58(2): 117–26PubMedCrossRefGoogle Scholar
  28. 28.
    Nakashima MN, Kataoka Y, Yamashita K, et al. Histological evidence for neuroprotective action of nebracetam on ischemic neuronal injury in the hippocampus of strokeprone spontaneously hypertensive rats. Jpn J Pharmacol 1995 Jan; 67(1): 91–4PubMedCrossRefGoogle Scholar
  29. 29.
    Krause W, Kühne G, Matthes H. Pharmacokinetics of the antidepressant rolipram in healthy volunteers. Xenobiotica 1989 Jun; 19(6): 683–92PubMedCrossRefGoogle Scholar
  30. 30.
    Fleischhacker WW, Hinterhuber H, Bauer H, et al. A multicenter double-blind study of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram in patients with major depressive disorder. Neuropsychobiology 1992; 26(1–2): 59–64PubMedCrossRefGoogle Scholar
  31. 31.
    Mukai H, Sugimoto T, Ago M, et al. Pharmacokinetics of NS-105, a novel cognition enhancer. 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys after single administration of 14C-NS-105. Arzneimittelforschung 1999 Nov; 49(11): 881–90PubMedGoogle Scholar
  32. 32.
    Kumagai Y, Yokota S, Isawa S, et al. Comparison of pharmacokinetics of NS-105, a novel agent for cerebrovascular disease, in elderly and young subjects. Int J Clin Pharmacol Res 1999; 19(1): 1–8PubMedGoogle Scholar
  33. 33.
    Bessho T, Takashina K, Tabata R, et al. Effect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin -4-yl)acetoamide on deficits of water maze learning in rats. Arzneimittelforschung 1996 Apr; 46(4): 369–73PubMedGoogle Scholar
  34. 34.
    Bessho T, Takashina K, Eguchi J, et al. MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated rats. J Neural Transm 2008 Jul; 115(7): 1019–25PubMedCrossRefGoogle Scholar
  35. 35.
    Black A, Chang T. Metabolic disposition of Rolziracetam in laboratory animals. Eur J Drug Metab Pharmacokinet 1987 Apr–Jun; 12(2): 135–43PubMedCrossRefGoogle Scholar
  36. 36.
    Pinza M, Farina C, Cerri A, et al. Synthesis and pharmacological activity of a series of dihydro-1H-pyrrolo[1, 2-a]imidazole-2,5(3H,6H)-diones, a novel class of potent cognition enhancers. J Med Chem 1993 Dec 24; 36(26): 4214–20PubMedCrossRefGoogle Scholar
  37. 37.
    Farina C, Gagliardi S, Ghelardini C, et al. Synthesis and biological evaluation of novel dimiracetam derivatives useful for the treatment of neuropathic pain. Bioorg Med Chem 2008 Mar 15; 16(6): 3224–32PubMedCrossRefGoogle Scholar
  38. 38.
    Copani A, Genazzani AA, Aleppo G, et al. Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures. J Neurochem 1992 Apr; 58(4): 1199–204PubMedCrossRefGoogle Scholar
  39. 39.
    Pugsley TA, Shih Y-H, Coughenour L, et al. Some neurochemical properties of pramiracetam (CI-879), a new cognition-enhancing agent. Drug Dev Res 1983; 3: 407–20CrossRefGoogle Scholar
  40. 40.
    Kovalev GI, Akhapkina VI, Abaimov DA, et al. Phenotropil as receptor modulator of synaptic neurotransmission [in Russian]. Nervnye Bolezni 2007; 4: 22–6Google Scholar
  41. 41.
    Carunchio I, Pieri M, Ciotti MT, et al. Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. Epilepsia 2007 Apr; 48(4): 654–62PubMedCrossRefGoogle Scholar
  42. 42.
    Lukyanetz EA, Shkryl VM, Kostyuk PG. Selective blockade of N-type calcium channels by levetiracetam. Epilepsia 2002 Jan; 43(1): 9–18PubMedCrossRefGoogle Scholar
  43. 43.
    Pisani A, Bonsi P, Martella G, et al. Intracellular calcium increase in epileptiform activity: modulation by levetiracetam and lamotrigine. Epilepsia 2004 Jul; 45(7): 719–28PubMedCrossRefGoogle Scholar
  44. 44.
    Lynch BA, Lambeng N, Nocka K, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A 2004 Jun; 101(26): 9861–6PubMedCrossRefGoogle Scholar
  45. 45.
    Moriguchi S, Shioda N, Maejima H, et al. Nefiracetam potentiates N-methyl-D-aspartate (NMDA) receptor function via protein kinase C activation and reduces magnesium block of NMDA receptor. Mol Pharmacol 2007 Feb;71(2): 580–7PubMedCrossRefGoogle Scholar
  46. 46.
    Kataoka Y, Niwa M, Koizumi S, et al. Nebracetam (WEB 1881FU) prevents N-methyl-D-aspartate receptor-mediated neurotoxicity in rat striatal slices. Jpn J Pharmacol 1992 Jun; 59(2): 247–50PubMedCrossRefGoogle Scholar
  47. 47.
    Kataoka Y, Kohno Y, Watanabe Y. Inhibitory action of nebracetam on various stimuli-evoked increases in intracellular Ca2+ concentrations in cultured rat cerebellar granule cells. Jpn J Pharmacol 1995 Jan; 67(1): 87–90PubMedCrossRefGoogle Scholar
  48. 48.
    Oka M, Itoh Y, Tatsumi S, et al. A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture. Naunyn Schmiedebergs Arch Pharmacol 1997 Aug; 356(2): 189–96PubMedCrossRefGoogle Scholar
  49. 49.
    Oka M, Itoh Y, Shimidzu T, et al. Involvement of metabotropic glutamate receptors in Gi- and Gs-dependent modulation of adenylate cyclase activity induced by a novel cognition enhancer NS-105 in rat brain. Brain Res 1997 Apr 18; 754(1–2): 121–30PubMedCrossRefGoogle Scholar
  50. 50.
    Shimidzu T, Itoh Y, Oka M, et al. Effect of a novel cognition enhancer NS-105 on learned helplessness in rats: possible involvement of GABA(B) receptor up-regulation after repeated treatment. Eur J Pharmacol 1997 Nov 12; 338(3): 225–32PubMedCrossRefGoogle Scholar
  51. 51.
    Takashina K, Bessho T, Mori R, et al. MKC-231, a choline uptake enhancer: (3) mode of action of MKC-231 in the enhancement of high-affinity choline uptake. J Neural Transm 2008 Jul; 115(7): 1037–46PubMedCrossRefGoogle Scholar
  52. 52.
    Takashina K, Bessho T, Mori R, et al. MKC-231, a choline uptake enhancer: (2) effect on synthesis and release of acetylcholine in AF64A-treated rats. J Neural Transm 2008 Jul; 115(7): 1027–35PubMedCrossRefGoogle Scholar
  53. 53.
    Fedi M, Reutens D, Dubeau F, et al. Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy. Arch Neurol 2001 May; 58(5): 781–6PubMedCrossRefGoogle Scholar
  54. 54.
    Holinski S, Claus B, Alaaraj N, et al. Cerebroprotective effect of piracetam in patients undergoing coronary bypass burgery. Med Sci Monit 2008 Nov; 14(11): PI53–7PubMedGoogle Scholar
  55. 55.
    Uebelhack R, Vohs K, Zytowski M, et al. Effect of piracetam on cognitive performance in patients undergoing bypass surgery. Pharmacopsychiatry 2003 May; 36(3): 89–93PubMedCrossRefGoogle Scholar
  56. 56.
    Szalma I, Kiss A, Kardos L, et al. Piracetam prevents cognitive decline in coronary artery bypass: a randomized trial versus placebo. Ann Thorac Surg 2006 Oct; 82(4): 1430–5PubMedCrossRefGoogle Scholar
  57. 57.
    Batysheva TT, Bagir LV, Kostenko EV, et al. Experience of the out-patient use of memotropil in the treatment of cognitive disorders in patients with chronic progressive cerebrovascular disorders. Neurosci Behav Physiol 2009 Feb; 39(2): 193–7PubMedCrossRefGoogle Scholar
  58. 58.
    Neznamov GG, Teleshova ES. Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin. Neurosci Behav Physiol 2009 Mar; 39(3): 311–21PubMedCrossRefGoogle Scholar
  59. 59.
    Zavadenko NN, Guzilova LS. Sequelae of closed cranio-cerebral trauma and the efficacy of piracetam in its treatment in adolescents. Neurosci Behav Physiol 2009 May; 39(4): 323–8PubMedCrossRefGoogle Scholar
  60. 60.
    Jelic V, Kivipelto M, Winblad B. Clinical trials in mild cognitive impairment: lessons for the future. J Neurol Neurosurg Psychiatry 2006 Apr; 77(4): 429–38PubMedCrossRefGoogle Scholar
  61. 61.
    UCB, Inc. Efficacy and safety of piracetam taken for 12 months in subjects suffering from mild cognitive impairment (MCI) [ identifier NCT00567060]. US National Institutes of Health, [online]. Available from URL: [Accessed 2010 Jan 22]
  62. 62.
    Libov I, Miodownik C, Bersudsky Y, et al. Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study. J Clin Psychiatry 2007 Jul; 68(7): 1031–7PubMedCrossRefGoogle Scholar
  63. 63.
    Beersheva Mental Health Center. Piracetam for treatment tardive dyskinesia [ identifier NCT001 90008]. US National Institutes of Health, ClinicalTrials. gov [online]. Available from URL: [Accessed 2010 Jan 22]
  64. 64.
    Ince Gunal D, Agan K, Afsar N, et al. The effect of piracetam on ataxia: clinical observations in a group of autosomal dominant cerebellar ataxia patients. J Clin Pharm Ther 2008 Apr; 33(2): 175–8PubMedCrossRefGoogle Scholar
  65. 65.
    Kessler J, Thiel A, Karbe H, et al. Piracetam improves activated blood flow and facilitates rehabilitation of poststroke aphasic patients. Stroke 2000 Sep; 31(9): 2112–6PubMedCrossRefGoogle Scholar
  66. 66.
    Kampman K, Majewska MD, Tourian K, et al. A pilot trial of piracetam and ginkgo biloba for the treatment of cocaine dependence. Addic Behav 2003 Apr; 28(3): 437–48CrossRefGoogle Scholar
  67. 67.
    National Institute on Drug Abuse (NIDA). Piracetam for treatment of cocaine addiction — 3 [ identifier NCT00000198]. US National Institutes of Health, [online]. Available from URL: [Accessed 2010 Jan 22]
  68. 68.
    National Institute on Drug Abuse (NIDA). Piracetam for treatment of cocaine addiction, phase II — 4 [ identifier NCT00000199]. US National Institutes of Health, [online]. Available from URL: [Accessed 2010 Jan 22]
  69. 69.
    Boiko AN, Batysheva TT, Matvievskaya OV, et al. Characteristics of the formation of chronic fatigue syndrome and approaches to its treatment in young patients with focal brain damage. Neurosci Behav Physiol 2007 Mar; 37(3): 221–8PubMedCrossRefGoogle Scholar
  70. 70.
    Akhondzadeh S, Tajdar H, Mohammadi MR, et al. A double-blind placebo controlled trial of piracetam added to risperidone in patients with autistic disorder. Child Psychiatry Hum Dev 2008 Sep; 39(3): 237–45PubMedCrossRefGoogle Scholar
  71. 71.
    Butler DE, Leonard JD, Caprathe BW, et al. Amnesia-reversal activity of a series of cyclic imides. J Med Chem 1987 Mar; 30(3): 498–503PubMedCrossRefGoogle Scholar
  72. 72.
    Tang WK, Ungvari GS, Leung HC. Effect of piracetam on ECT-induced cognitive disturbances: a randomized, placebo-controlled, double-blind study. J ECT 2002 Sep; 18(3): 130–7PubMedCrossRefGoogle Scholar
  73. 73.
    Lobaugh NJ, Karaskov V, Rombough V, et al. Piracetam therapy does not enhance cognitive functioning in children with Down syndrome. Arch Pediatr Adolesc Med 2001 Apr; 155(4): 442–8PubMedGoogle Scholar
  74. 74.
    Ricci S, Celani MG, Cantisani TA, et al. Piracetam in acute stroke: a systematic review. J Neurol 2000 Apr; 247(4): 263–6PubMedCrossRefGoogle Scholar
  75. 75.
    Ovanesov KB, Shikina IB, Arushanian EB, et al. Effect of pyracetam on the color discriminative function of retina in patients with craniocerebral trauma [in Russian]. Eksp Klin Farmakol 2003 Jul–Aug; 66(4): 6–8PubMedGoogle Scholar
  76. 76.
    Kiseleva TN, Lagutina IuM, Kravchuk EA. Effect of fezam on ocular dynamics in patients with senile macular degeneration [in Russian]. Vestn Oftalmol 2005 Jul–Aug; 121(4): 26–8PubMedGoogle Scholar
  77. 77.
    Preda L, Alberoni M, Bressi S, et al. Effects of acute doses of oxiracetam in the scopolamine model of human amnesia. Psychopharmacology (Berl) 1993; 110(4): 421–6CrossRefGoogle Scholar
  78. 78.
    Rozzini R, Zanetti O, Bianchetti A. Treatment of cognitive impairment secondary to degenerative dementia: effectiveness of oxiracetam therapy. Acta Neurol (Napoli) 1993 Feb; 15(1): 44–52Google Scholar
  79. 79.
    Green RC, Goldstein FC, Auchus AP, et al. Treatment trial of oxiracetam in Alzheimer’s disease. Arch Neurol 1992 Nov;49(11): 1135–6PubMedCrossRefGoogle Scholar
  80. 80.
    Biogenesis Laboratories. Product information: pramiracetam (Neupramir) [online]. Available from URL: [Accessed 2010 Jan 22]
  81. 81.
    McLean Jr A, Cardenas DD, Burgess D, et al. Placebo-controlled study of pramiracetam in young males with memory and cognitive problems resulting from head injury and anoxia. Brain Inj 1991 Oct–Dec; 5(4): 375–80PubMedCrossRefGoogle Scholar
  82. 82.
    Mauri M, Sinforiani E, Reverberi F, et al. Pramiracetam effects on scopolamine-induced amnesia in healthy volunteers. Arch Gerontol Geriatr 1994 Mar–Apr; 18(2): 133–9PubMedCrossRefGoogle Scholar
  83. 83.
    Dziak LA, Golik VA, Miziakina EV. Experience in the application of pramistar, a new nootropic preparation, in the treatment of memory disorders in patients with cerebrovascular pathology [in Russian]. Lik Sprava 2003 Dec; (8): 67–72Google Scholar
  84. 84.
    Tkachev AV. atApplication of nootropic agents in complex treatment of patients with concussion of the brain [in Russian]. Lik Sprava 2007 Jul–Sep; (5–6): 82-5Google Scholar
  85. 85.
    Savchenko AIu, Zakharova NS, Stepanov IN. The phenotropil treatment of the consequences of brain organic lesions [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova 2005; 105(12): 22–6PubMedGoogle Scholar
  86. 86.
    Kalinsky PP, Nazarov W. Use of phenotropil in the treatment of asthenic syndrome and autonomic disturbances in the acute period of mild cranial brain trauma [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova 2007; 107(2): 61–3Google Scholar
  87. 87.
    Gustov AA, Smirnov AA, Korshunova IuA, et al. Phenotropil in the treatment of vascular encephalopathy [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova 2006; 106(3): 52–3PubMedGoogle Scholar
  88. 88.
    Sazonov DV, Ryabukhina OV, Bulatova EV, et al. Use of phenotropil in complex treatment of multiple sclerosis [in Russian]. Nervnye Bolezni 2006; 4: 18–21Google Scholar
  89. 89.
    Akhapkina VI, Fedin AI, Avedisova AS, et al. Efficacy of Phenotropil for treatment of astenic and chronic fatigue syndromes [in Russian]. Nervnye Bolezni 2004; 3: 28–32Google Scholar
  90. 90.
    Zvonareva EV. Phenotropil in the therapy of cognitive disorders in teenagers with astenic syndrome [in Russian]. Nervnye Bolezni 2006; 2: 27–8Google Scholar
  91. 91.
    Bel’skaia GN, Ponomareva IV, Lukashevich IG, et al. Complex treatment of epilepsy with phenotropil [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova 2007; 107(8): 40–3PubMedGoogle Scholar
  92. 92.
    Lybzikova GN, Iaglova ZhS, Kharlamova IuS. The efficacy of phenotropil in the complex treatment of epilepsy [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova 2008; 108(2): 69–70PubMedGoogle Scholar
  93. 93.
    Gerasimova MM, Chichanovskaia LV, Slezkina LA. The clinical and immunological aspects of the effects of phenotropil on consequences of stroke [in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova 2005; 105(5): 63–4PubMedGoogle Scholar
  94. 94.
    Bagir LV, Batysheva TT, Boiko AN, et al. Use of phenotropil for early treatment of patients after stroke [in Russian]. Concilium Medicum 2006; 8(8): 96–101Google Scholar
  95. 95.
    Basinskii SN, Basinskii AS. Neuroprotective effect of Fenotropil in unstabilized primary glaucoma [in Russian]. Russkii Med Zh 2007; 8(4): 148–51Google Scholar
  96. 96.
    Robinson RG, Jorge RE, Clarence-Smith K. Double-blind randomized treatment of poststroke depression using nefiracetam. J Neuropsychiatry Clin Neurosci 2008 Spring; 20(2): 178–84PubMedCrossRefGoogle Scholar
  97. 97.
    Robinson RG, Jorge RE, Clarence-Smith K, et al. Double-blind treatment of apathy in patients with poststroke depression using nefiracetam. J Neuropsychiatry Clin Neurosci 2009 Spring; 21(2): 144–51PubMedCrossRefGoogle Scholar
  98. 98.
    National Institutes of Health Clinical Center (CC). Nefiracetam in the treatment of Alzheimer’s disease [ identifier NCT00001933]. US National Institutes of Health, [online]. Available from URL: [Accessed 2010 Jan 22]
  99. 99.
    National Institutes of Health Clinical Center (CC). Anti-depressant effects on cAMP specific phosphodiesterase (PDE4) in depressed patients [ identifier NCT00369798]. US National Institutes of Health, [online]. Available from URL: [Accessed 2010 Jan 22]
  100. 100.
    National Institutes of Health Clinical Center (CC). Rolipram to treat multiple sclerosis [ identifier NCT00011375]. US National Institutes of Health, [online]. Available from URL: [Accessed 2010 Jan 22]
  101. 101.
    Bielekova B, Richert N, Howard T, et al. Treatment with the phosphodiesterase type-4 inhibitor rolipram fails to inhibit blood: brain barrier disruption in multiple sclerosis. Mult Scler 2009 Oct; 15(10): 1206–14PubMedCrossRefGoogle Scholar
  102. 102.
    Ogiso T, Iwaki M, Tanino T, et al. Pharmacokinetics of aniracetam and its metabolites in rats. J Pharm Sci 1998 May; 87(5): 594–8PubMedCrossRefGoogle Scholar
  103. 103.
    Senin U, Abate G, Fieschi C, et al. Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study. Eur Neuropsychopharmacol 1991 Dec; 1(4): 511–7PubMedCrossRefGoogle Scholar
  104. 104.
    Canonico V, Forgione L, Paoletti C, et al. Efficacy and tolerance of aniracetam in elderly patients with primary or secondary mental deterioration [in Italian]. Riv Neurol 1991 May-Jun; 61(3): 92–6PubMedGoogle Scholar
  105. 105.
    Somnier FE, Ostergaard MS, Boysen G, et al. Aniracetam tested in chronic psychosyndrome after long-term exposure to organic solvents: a randomized, double-blind, placebo-controlled cross-over study with neuropsychological tests. Psychopharmacology (Berl) 1990; 101(1): 43–6CrossRefGoogle Scholar
  106. 106.
    Bobkov IuG, Morozov IS, Glozman OM, et al. Pharmacological characteristics of a new phenyl analog of piracetam-4-phenylpiracetam [in Russian]. Biull Eksp Biol Med 1983 Apr; 95(4): 50–3PubMedCrossRefGoogle Scholar
  107. 107.
    Bialer M, Johannessen SI, Kupferberg HJ, et al. Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII). Epilepsy Res 2007 Jan; 73(1): 1–52PubMedCrossRefGoogle Scholar
  108. 108.
    Rogawski MA. Brivaracetam: a rational drug discovery success story. Br J Pharmacol 2008 Aug; 154(8): 1555–7PubMedCrossRefGoogle Scholar
  109. 109.
    Pollard JR. Seletracetam, a small molecule SV2A modulator for the treatment of epilepsy. Curr Opin Investig Drugs 2008 Jan; 9(1): 101–7PubMedGoogle Scholar
  110. 110.
    Sirsi D, Safdieh JE. The safety of levetiracetam. Expert Opin Drug Saf 2007 May; 6(3): 241–50PubMedCrossRefGoogle Scholar
  111. 111.
    Nissen-Meyer LS, Svalheim S, Taubøll E, et al. How can antiepileptic drugs affect bone mass, structure and metabolism? Lessons from animal studies. Seizure 2008 Mar; 17(2): 187–91PubMedCrossRefGoogle Scholar
  112. 112.
    Carreno M. Levetiracetam. Drugs Today (Barc) 2007 Nov; 43(11): 769–94CrossRefGoogle Scholar
  113. 113.
    Zhou B, Zhang Q, Tian L, et al. Effects of levetiracetam as an add-on therapy on cognitive function and quality of life in patients with refractory partial seizures. Epilepsy Behav 2008 Feb; 12(2): 305–10PubMedCrossRefGoogle Scholar
  114. 114.
    Kossoff EH, Los JG, Boatman DF. A pilot study transitioning children onto levetiracetam monotherapy to improve language dysfunction associated with benign rolandic epilepsy. Epilepsy Behav 2007 Dec; 11(4): 514–7PubMedCrossRefGoogle Scholar
  115. 115.
    Kinrys G, Wygant LE, Pardo TB, et al. Levetiracetam for treatment-refractory posttraumatic stress disorder. J Clin Psychiatry 2006 Feb; 67(2): 211–4PubMedCrossRefGoogle Scholar
  116. 116.
    Simon NM, Worthington JJ, Doyle AC, et al. An open-label study of levetiracetam for the treatment of social anxiety disorder. J Clin Psychiatry 2004 Sep; 65(9): 1219–22PubMedCrossRefGoogle Scholar
  117. 117.
    Mazza M, Martini A, Scoppetta M, et al. Effect of levetiracetam on depression and anxiety in adult epileptic patients. Prog Neuropsychopharmacol Biol Psychiatry 2008 Feb 15; 32(2): 539–43PubMedCrossRefGoogle Scholar
  118. 118.
    Wasserman S, Iyengar R, Chaplin WF, et al. Levetiracetam versus placebo in childhood and adolescent autism: a double-blind placebo-controlled study. Int Clin Psycho-pharmacol 2006 Nov; 21(6): 363–7CrossRefGoogle Scholar
  119. 119.
    Brown ES, Frol AB, Khan DA, et al. Impact of levetiracetam on mood and cognition during prednisone therapy. Eur Psychiatry 2007 Oct; 22(7): 448–52PubMedCrossRefGoogle Scholar
  120. 120.
    Malawska B, Kulig K. Brivaracetam: a new drug in development for epilepsy and neuropathic pain. Expert Opin Investig Drugs 2008 Mar; 17(3): 361–9PubMedCrossRefGoogle Scholar
  121. 121.
    French J, von Rosenstiel P. Efficacy and tolerability of brivaracetam as adjunctive treatment for adults with refractory partial-onset seizures [abstract]. Epilepsia 2007; 48 Suppl. 7: 78Google Scholar
  122. 122.
    van Paesschen W, von Rosenstiel P. Efficacy and tolerability of brivaracetam as adjunctive treatment for adults with refractory partial-onset epilepsy. Epilepsia 2007; 48 Suppl. 7: 56–7Google Scholar
  123. 123.
    Narahashi T, Moriguchi S, Zhao X, et al. Mechanisms of action of cognitive enhancers on neuroreceptors. Biol Pharm Bull 2004 Nov; 27(11): 1701–6PubMedCrossRefGoogle Scholar
  124. 124.
    Münte TF, Heinze HJ, Scholz M, et al. Effects of a cholinergic nootropic (WEB 1881 FU) on event-related potentials recorded in incidental and intentional memory tasks. Neuropsychobiology 1988; 19(3): 158–68PubMedCrossRefGoogle Scholar
  125. 125.
    Münte TF, Heinze HJ, Scholz MB, et al. Event-related potentials and visual spatial attention: influence of a cholinergic drug. Neuropsychobiology 1989; 21(2): 94–9PubMedCrossRefGoogle Scholar
  126. 126.
    Urakami K, Shimomura T, Ohshima T, et al. Clinical effect of WEB 1881 (nebracetam fumarate) on patients with dementia of the Alzheimer type and study of its clinical pharmacology. Clin Neuropharmacol 1993 Aug; 16(4): 347–58PubMedCrossRefGoogle Scholar
  127. 127.
    Scott AI, Perini AF, Shering PA, et al. In-patient major depression: is rolipram as effective as amitriptyline? Eur J Clin Pharmacol 1991; 40(2): 127–9PubMedCrossRefGoogle Scholar
  128. 128.
    Ross CE, Toon S, Rowland M, et al. A study to assess the anticholinergic activity of rolipram in healthy elderly volunteers. Pharmacopsychiatry 1988 Sep; 21(5): 222–5PubMedCrossRefGoogle Scholar
  129. 129.
    Hebenstreit GF, Fellerer K, Fichte K, et al. Rolipram in major depressive disorder: results of a double-blind comparative study with imipramine. Pharmacopsychiatry 1989 Jul; 22(4): 156–60PubMedCrossRefGoogle Scholar
  130. 130.
    Bertolino A, Crippa D, di Dio S, et al. Rolipram versus imipramine in inpatients with major, “minor” or atypical depressive disorder: a double-blind double-dummy study aimed at testing a novel therapeutic approach. Int Clin Psychopharmacol 1988 Jul; 3(3): 245–53PubMedCrossRefGoogle Scholar
  131. 131.
    Nikulina E, Tidwell JL, Dai HN, et al. The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci USA 2004 Jun 8; 101(23): 8786–90PubMedCrossRefGoogle Scholar
  132. 132.
    Kajana S, Goshgarian HG. Administration of phosphodiesterase inhibitors and an adenosine A1 receptor antagonist induces phrenic nerve recovery in high cervical spinal cord injured rats. Exp Neurol 2008 Apr; 210(2): 671–80PubMedCrossRefGoogle Scholar
  133. 133.
    Nagakura A, Niimura M, Takeo S. Effects of a phospho-diesterase IV inhibitor rolipram on microsphere embolism-induced defects in memory function and cerebral cyclic AMP signal transduction system in rats. Br J Pharmacol 2002 Apr; 135(7): 1783–93PubMedCrossRefGoogle Scholar
  134. 134.
    Mukai H, Sugimoto T, Ago M, et al. Pharmacokinetics of NS-105, a novel cognition enhancer. 2nd communication: distribution and transfer into fetus and milk after single administration, and effects of repeated administration on pharmacokinetics and hepatic drug-metabolizing enzyme activities in rats. Arzneimittelforschung 1999 Dec; 49(12): 977–85PubMedGoogle Scholar
  135. 135.
    Newpher TM, Ehlers MD. Glutamate receptor dynamics in dendritic microdomains. Neuron 2008 May 22; 58(4): 472–97PubMedCrossRefGoogle Scholar
  136. 136.
    Palucha A, Pilc A. Metabotropic glutamate receptor ligands as possible anxiolytic and antidepressant drugs. Pharmacol Ther 2007 Jul; 115(1): 116–47PubMedCrossRefGoogle Scholar
  137. 137.
    Neugebauer V. Glutamate receptor ligands. Handb Exp Pharmacol 2007; 177: 217–49PubMedCrossRefGoogle Scholar
  138. 138.
    Antonelli T, Fuxe K, Tomasini MC, et al. Neurotensin receptor mechanisms and its modulation of glutamate transmission in the brain: relevance for neurodegenerative diseases and their treatment. Prog Neurobiol 2007 Oct; 83(2): 92–109PubMedCrossRefGoogle Scholar
  139. 139.
    Abdipranoto A, Wu S, Stayte S, et al. The role of neurogenesis in neurodegenerative diseases and its implications for therapeutic development. CNS Neurol Disord Drug Targets 2008 Apr; 7(2): 187–210PubMedCrossRefGoogle Scholar
  140. 140.
    Hoyt KR, Arden SR, Aizenman E, et al. Reverse Na+/Ca2+ exchange contributes to glutamate-induced intracellular Ca2+ concentration increases in cultured rat forebrain neurons. Mol Pharmacol 1998 Apr; 53(4): 742–9PubMedGoogle Scholar
  141. 141.
    Araújo IM, Carreira BP, Pereira T, et al. Changes in calcium dynamics following the reversal of the sodium-calcium exchanger have a key role in AMPA receptor-mediated neurodegeneration via calpain activation in hippocampal neurons. Cell Death Differ 2007 Sep; 4(9): 1635–46CrossRefGoogle Scholar
  142. 142.
    Mansouri B, Henne WM, Oomman SK, et al. Involvement of calpain in AMPA-induced toxicity to rat cerebellar Purkinje neurons. Eur J Pharmacol 2007 Feb; 557(2–3): 106–14PubMedCrossRefGoogle Scholar
  143. 143.
    Mattson MP. Calcium and neurodegeneration. Aging Cell 2007 Jun; 6(3): 337–50PubMedCrossRefGoogle Scholar
  144. 144.
    Lankiewicz S, Marc Luetjens C, Truc Bui N, et al. Activation of calpain I converts excitotoxic neuron death into a caspase-independent cell death. J Biol Chem 2000 Jun 2; 275(22): 17064–71PubMedCrossRefGoogle Scholar
  145. 145.
    Bird CM, Burgess N. The hippocampus and memory: insights from spatial processing. Nat Rev Neurosci 2008 Mar; 9(3): 182–94PubMedCrossRefGoogle Scholar
  146. 146.
    Neves G, Cooke SF, Bliss TV. Synaptic plasticity, memory and the hippocampus: a neural network approach to causality. Nat Rev Neurosci 2008 Jan; 9(1): 65–75PubMedCrossRefGoogle Scholar
  147. 147.
    Scheff SW, Price DA. Alzheimer’s disease-related alterations in synaptic density: neocortex and hippocampus. J Alzheimers Dis 2006; 9 (3 Suppl.): 101–15PubMedGoogle Scholar
  148. 148.
    Chiechio S, Copani A, Gereau 4th RW, et al. Acetyl-L-carnitine in neuropathic pain: experimental data. CNS Drugs 2007; 21 Suppl. 1: 31–8CrossRefGoogle Scholar
  149. 149.
    Barhwal K, Singh SB, Hota SK, et al. Acetyl-L-carnitine ameliorates hypobaric hypoxic impairment and spatial memory deficits in rats. Eur J Pharmacol 2007 Sep; 570(1-3): 97–107PubMedCrossRefGoogle Scholar
  150. 150.
    Zou X, Sadovova N, Patterson TA, et al. The effects of L-carnitine on the combination of, inhalation anesthetic-induced developmental, neuronal apoptosis in the rat frontal cortex. Neuroscience 2008 Feb; 151(4): 1053–65PubMedCrossRefGoogle Scholar
  151. 151.
    Schaeffer EL, Gattaz WF. Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme. Psychopharmacology (Berl) 2008 May; 198(1): 1–27CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  1. 1.NovoMed ConsultingSilver SpringUSA

Personalised recommendations