The nootropic concept and its prospective implications
Abstract
Giurgea, C.E.: The nootropic concept and its prospective implications. Drug. Dev. Res. 2:441–446, 1982.
The nootropic concept emerged about 10 years ago essentially from the unusual pharmacology of piracetam, which later on was confirmed and extended to human pharmacoclinics and therapeutics. A nootropic drug is characterized by a direct functional activation of the higher integrative brain mechanisms that enhances cortical vigilance, a telencephalic functional selectivity, and a particular efficiency in restoring deficient higher nervous activity. In contradistinction to other psychotropic drugs, nootropics do not induce direct reticular, limbic, or other subcortical events. Little is known with regard to nootropic, neurochemical mechanisms of action except that they interact with factors that contribute to the neuronal membrane stability, and possibly with the brain 5‐HT. Main therapeutical indications seem to be in children with speech disorders, in the posttraumatic, and posthypoxic sequelae, in vertigo of central origin, and in geriatric, moderately impaired, possibly dysmnesic patients. Other drugs, such as pyritinol, meclofenoxate, and, to some extent, hydergine and vincamine, do show partially nootropic activities. The nootropic line of research is by now multifaceted to deepen the neurochemical and neurophysiologic comprehension of nootropics' mode of action; to make clearer their clinical differential profile; to enlarge the nootropic framework to some other existing drugs, clinically if not pharmacologically related to piracetam; and to find new, more potent, and possibly more selective nootropic agents. The general aim of nootropic research is to find new drugs capable of enhancing directly the efficiency of the cognitive, noetic activity of the brain, thus compensating various neuro‐psychologic deficits such as, but not exclusively, those related to aging.
Number of times cited: 58
- Norbert Jaušovec and Anja Pahor, Other Approaches: From Neurofeedback to Cognitive-Enhancing Drugs, Increasing Intelligence, 10.1016/B978-0-12-809407-5.00005-1, (237-316), (2017).
- O Karpukhina, K Gumargalieva, S Bokieva and A Inozemtsev, A COMMENTARY ON STRUCTURAL TRANSFORMATIONS OF PIRACETAM UNDER LEAD ACETATE INFLUENCE, Chemical Technology, 10.1201/b18178-17, (199-206), (2015).
- Ashish K. Mehta, Yogendra Bhati, Chakra D. Tripathi and Krishna K. Sharma, Analgesic Effect of Piracetam on Peripheral Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats, Neurochemical Research, 39, 8, (1433), (2014).
- Sonam Gupta, Dinesh Kumar Verma, Joyshree Biswas, K. Siva Rama Raju, Neeraj Joshi, Wahajuddin and Sarika Singh, The metabolic enhancer piracetam attenuates mitochondrion-specific endonuclease G translocation and oxidative DNA fragmentation, Free Radical Biology and Medicine, 73, (278), (2014).
- Prabhat Kosta, Ashish K. Mehta, Amit K. Sharma, Naresh Khanna, Pramod K. Mediratta, Dharmendra R. Mundhada and Sanvidhan Suke, Effect of piracetam and vitamin E on phosphamidon-induced impairment of memory and oxidative stress in rats, Drug and Chemical Toxicology, 36, 1, (48), (2013).
- Carola Stockburger, Christopher Kurz, Konrad A. Koch, Schamim H. Eckert, Kristina Leuner and Walter E. Müller, Improvement of mitochondrial function and dynamics by the metabolic enhancer piracetam, Biochemical Society Transactions, 41, 5, (1331), (2013).
- C Kurz, I Ungerer, U Lipka, S Kirr, T Schütt, A Eckert, K Leuner and WE Müller, The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by ß‐amyloid peptide, British Journal of Pharmacology, 160, 2, (246-257), (2010).
- Sparsh Gupta, Gobind Rai Garg, Nidhi Bharal, P.K. Mediratta, B.D. Banerjee and K.K. Sharma, Reversal of propoxur-induced impairment of step-down passive avoidance, transfer latency and oxidative stress by piracetam and ascorbic acid in rats, Environmental Toxicology and Pharmacology, 28, 3, (403), (2009).
- Uta Keil, Isabel Scherping, Susanne Hauptmann, Katin Schuessel, Anne Eckert and Walter E Müller, Piracetam improves mitochondrial dysfunction following oxidative stress, British Journal of Pharmacology, 147, 2, (199-208), (2009).
- Yutaka Kitano, Chika Komiyama, Mitsuhiro Makino, Kiyoshi Takasuna, Akira Takazawa and Shinobu Sakurada, Anticonvulsant Properties of the Novel Nootropic Agent Nefiracetam in Seizure Models of Mice and Rats, Epilepsia, 46, 6, (811-818), (2005).
- Yutaka Kitano, Chika Komiyama, Mitsuhiro Makino, Yoshio Kasai, Kiyoshi Takasuna, Masakazu Kinoshita, Osamu Yamazaki, Akira Takazawa, Toshio Yamauchi and Shinobu Sakurada, Effects of Nefiracetam, a Novel Pyrrolidone‐type Nootropic Agent, on the Amygdala‐kindled Seizures in Rats, Epilepsia, 46, 10, (1561-1568), (2005).
- YURIE NAKAMOTO, TADASHI SHIOTANI, SHIGEO WATABE, TOSHITAKA NABESHIMA and MITSUNOBU YOSHII, Nootropic Nefiracetam Inhibits Proconvulsant Action of Peripheral‐Type Benzodiazepines in Epileptic Mutant EL Mice, Annals of the New York Academy of Sciences, 1025, 1, (135-139), (2006).
- MITSUNOBU YOSHII, TAIJI FURUKAWA, YOSHIYASU OGIHARA, SHIGEO WATABE, TADASHI SHIOTANI, YASURO ISHIKAWA, MASAO NISHIMURA and TOSHIHIDE NUKADA, Negative Regulation of Opioid Receptor‐G Protein‐Ca2+ Channel Pathway by the Nootropic Nefiracetam, Annals of the New York Academy of Sciences, 1025, 1, (389-397), (2006).
- Mitsunobu Yoshii, Shigeo Watabe, Yoshiya L. Murashima, Toshihide Nukada, Tadashi Shiotani and Tomoyuki Nishizaki, Neuronal Ca2+ Channels and Nicotinic ACh Receptors as Functional Targets of the Nootropic Nefiracetam, Psychogeriatrics, 1, 1, (39-49), (2007).
- Julia Vaglenova and Vesselin Vesselinov Petkov, Can nootropic drugs be effective against the impact of ethanol teratogenicity on cognitive performance?, European Neuropsychopharmacology, 11, 1, (33), (2001).
- Tadashi Shiotani, Yurie Nakamoto, Shigeo Watabe, Mitsunobu Yoshii and Toshitaka Nabeshima, Anticonvulsant actions of nefiracetam on epileptic EL mice and their relation to peripheral-type benzodiazepine receptors, Brain Research, 859, 2, (255), (2000).
- Robert Zaczek and Robert J. Chorvat, Memory‐Enhancing Drugs, Kirk‐Othmer Encyclopedia of Chemical Technology, (2000).
- Marie‐Christine Dubroeucq, Jean‐Marie Stutzmann, Franco Manfré, Marc Capet and Georg Andrees Böhme, Psychopharmacological Agents, Ullmann's Encyclopedia of Industrial Chemistry, (2000).
- Mitsunobu Yoshii, Shigeo Watabe, Yoshiya L Murashima, Toshihide Nukada and Tadashi Shiotani, Cellular Mechanism of Action of Cognitive Enhancers: Effects of Nefiracetam on Neuronal Ca2+ Channels, Alzheimer Disease and Associated Disorders, 14, Supplement, (S95), (2000).
- Walter E. Müller, Sabrina Koch, Klaus Scheuer, Angelika Rostock and Reni Bartsch, Effects of piracetam on membrane fluidity in the aged mouse, rat, and human brain, Biochemical Pharmacology, 53, 2, (135), (1997).
- Mitsunobu Yoshii, Shigeo Watabe, Takeo Sakurai and Tadashi Shiotani, Cellular mechanisms underlying cognition-enhancing actions of nefiracetam (DM-9384), Behavioural Brain Research, 83, 1-2, (185), (1997).
- Flaminia Pavone, Mario Battaglia and Mario Sansone, Prevention of amitriptyline-induced avoidance impairment by tacrine in mice, Behavioural Brain Research, 89, 1-2, (229), (1997).
- A. Matton, S. Engelborghs, F. Bollengier, E. Finne and L. Vanhaeist, Modulating effect of the nootropic drug, piracetam on stress‐ and subsequent morphine‐induced prolactin secretion in male rats, British Journal of Pharmacology, 117, 3, (502-506), (2012).
- Kiyofumi Yamada and Toshitaka Nabeshima, Nefiracetam (DM‐9384): A Novel Antiamnesic Drug, CNS Drug Reviews, 2, 3, (322-342), (2006).
- TA Gudasheva, TA Voronina, RU Ostrovskaya, GG Rozantsev, NI Vasilevich, SS Trofimov, EV Kravchenko, AP Skoldinov and SB Seredenin, Synthesis and antiamnesic activity of a series of N-acylprolyl-containing dipeptides, European Journal of Medicinal Chemistry, 31, 2, (151), (1996).
- F. Brandão, A. Cadete-Leite, J.P. Andrade, M.D. Madeira and M.M. Paula-Barbosa, Piracetam promotes mossy fiber synaptic reorganization in rats withdrawn from alcohol, Alcohol, 13, 3, (239), (1996).
- T.A Gudasheva, S.S Boyko, V.Kh Akparov, R.U Ostrovskaya, S.P Skoldinov, G.G Rozantsev, T.A Voronina, V.P Zherdev and S.B Seredenin, Identification of a novel endogenous memory facilitating cyclic dipeptide cyclo‐prolylglycine in rat brain, FEBS Letters, 391, 1-2, (149-152), (1999).
- CHAO-SHENG HUANG, JENNY YAN MA, W MARSZALEC and T NARAHASHI, Effects of the Nootropic Drug Nefiracetam on the GABA A Receptor-channel Complex in Dorsal Root Ganglion Neurons, Neuropharmacology, 35, 9-10, (1251), (1996).
- Ciara Kelly and Robert Hunter, Current pharmacological strategies in Alzheimer's disease, International Journal of Geriatric Psychiatry, 10, 8, (633-646), (2004).
- F. Brandão, M.M. Paula-Barbosa and A. Cadete-Leite, Piracetam impedes hippocampal neuronal loss during withdrawal after chronic alcohol intake, Alcohol, 12, 3, (279), (1995).
- N.H.P. Allen and Alistair Burns, The treatment of Alzheimer's disease, Journal of Psychopharmacology, 9, 1, (43), (1995).
- S. STOLL, A. ROSTOCK, R. BARTSCH, E. KORN, A. MEICHELBÖCK and W. E. MÜLLER, The Potent Free Radical Scavenger α‐Lipoic Acid Improves Cognition in Rodents, Annals of the New York Academy of Sciences, 717, 1, (122-128), (2006).
- Alex Haahr Gouliaev and Alexander Senning, Piracetam and other structurally related nootropics, Brain Research Reviews, 19, 2, (180), (1994).
- K. N. Dudkin, V. K. Kruchinin and I. V. Chueva, An antioxidant-induced improvement in the cognitive characteristics of monkeys: Neurophysiological correlates in the visual cortex, Neuroscience and Behavioral Physiology, 24, 3, (289), (1994).
- Giuliano Bandoli, Alessandro Dolmella, Marino Nicolini and Francesco Tisato, X‐ray, NMR, and theoretical studies of the nootropic agent BMY‐21502, a pyrrolidinone derivative, Journal of Pharmaceutical Sciences, 83, 6, (878-882), (2006).
- Monika Jähkel, Jochen Oehler and Hans-Egbert Schumacher, Influence of nootropic and antidepressive drugs on open field and running wheel behavior in spontaneously high and low active mice, Pharmacology Biochemistry and Behavior, 49, 2, (263), (1994).
- Mitsunobu Yoshii and Shigeo Watabe, Enhancement of neuronal calcium channel currents by the nootropic agent, nefiracetam (DM-9384), in NG108-15 cells, Brain Research, 642, 1-2, (123), (1994).
- S. V. Krapivin, T. A. Voronina, N. N. Bogdanov and L. D. Smirnov, Neurophysiological analysis of the effects of nooglutil as opposed to known nootropic drugs, Pharmaceutical Chemistry Journal, 28, 4, (220), (1994).
- Shigeo Watabe, Hitoshi Yamaguchi and Shin-ichiro Ashida, DM-9384, a new cognition-enhancing agent, increases the turnover of components of the GABAergic system in the rat cerebral cortex, European Journal of Pharmacology, 238, 2-3, (303), (1993).
- A. Copani, A. A. Genazzani, G. Aleppo, G. Casabona, P. L. Canonico, U. Scapagnini and F. Nicoletti, Nootropic Drugs Positively Modulate α‐Amino‐3‐Hydroxy‐5‐Methyl‐4‐Isoxazolepropionic Acid‐Sensitive Glutamate Receptors in Neuronal Cultures, Journal of Neurochemistry, 58, 4, (1199-1204), (2006).
- Susan W. Miller, Janelle M. Mahoney and Michael W. Jann, Therapeutic Frontiers in Alzheimer's Disease, Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 12, 3, (217-231), (2012).
- Claudio Castellano, Mario Battaglia and Mario Sansone, Oxiracetam prevents haloperidol-induced passive avoidance impairment in mice, Pharmacology Biochemistry and Behavior, 42, 4, (797), (1992).
- L. Stoll, T. Schubert and W.E. Müller, Age-related deficits of central muscarinic cholinergic receptor function in the mouse: Partial restoration by chronic piracetam treatment, Neurobiology of Aging, 13, 1, (39), (1992).
- E. Chleide, J. Bruhwyler and M. Mercier, Enhanced resistance effect of piracetam upon hypoxia-induced impaired retention of fixed-interval responding in rats, Pharmacology Biochemistry and Behavior, 40, 1, (1), (1991).
- Martin Sarter, Taking stock of cognition enhancers, Trends in Pharmacological Sciences, 12, (456), (1991).
- Maria E. Amato, Giuliano Bandoli, Alessandro Dolmella, Antonio Grassi, Giuseppe C. Pappalardo and Emilio Toja, Molecular structures and conformations of 1-benzenesulphonyl-2-oxo-5-alkoxypyrrolidines with anti-amnesic activity, Journal of Molecular Structure, 245, 1-2, (81), (1991).
- Raymond T. Bartus, Drugs to Treat Age‐Related Neurodegenerative Problems The Final Frontier of Medical Science?, Journal of the American Geriatrics Society, 38, 6, (680-695), (2015).
- C. D. Nicholson, Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia, Psychopharmacology, 101, 2, (147), (1990).
- Maria E. Amato, Giuliano Bandoli, Umberto Casellato, Giuseppe C. Pappalardo and Emilio Toja, X-ray and 1H-NMR spectroscopic studies of the structures and conformations of the new nootropic agents RU-35929, RU-47010 and RU-35965, Journal of Molecular Structure, 238, (413), (1990).
- Mario Sansone and Alberto Oliverio, Avoidance facilitation by nootropics, Progress in Neuro-Psychopharmacology and Biological Psychiatry, 13, (S89), (1989).
- Cesare Mondadori, Thomas Ducret and Friedel Petschke, Blockade of the nootropic action of piracetam-like nootropics by adrenalectomy: an effect of dosage?, Behavioural Brain Research, 34, 1-2, (155), (1989).
- Carl Bredo Dahl and K. Gunnar Götestam, An Open Field Study of Antidepressant Drugs, Pharmacology & Toxicology, 64, 3, (302-307), (2009).
- Abdelkader Ennaceur, Albert Cavoy, Jean-Claude Costa and Jean Delacour, A new one-trial test for neurobiological studies of memory in rats. II: Effects of piracetam and pramiracetam, Behavioural Brain Research, 33, 2, (197), (1989).
- Joachim Schmidt, Hans‐Dieter Fischer and Christian Wustmann, Strategies and new aspects in the pharmacology of drugs for the treatment of senile dementia, Drug Development Research, 14, 3‐4, (251-262), (2004).
- A. Cavoy, A. Ennaceur and J. Delacour, Effects of piracetam on learned helplessness in rats, Physiology & Behavior, 42, 6, (545), (1988).
- Martine Ammassari-Teule, Francesca R. D'Amato, Mario Sansone and Alberto Oliverio, Avoidance facilitation in adult mice by prenatal administration of the nootropic drug oxiracetam, Pharmacological Research Communications, 18, 12, (1169), (1986).
- Virginia J. Galizia, Pharmacotherapy of Memory Loss in the Geriatric Patient, Drug Intelligence & Clinical Pharmacy, 18, 10, (784), (1984).
- Fred M. Hershenson and John G. Marriott, Chapter 4. Cognitive Disorders, , 10.1016/S0065-7743(08)60680-6, (31-40), (1984).




