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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.
... (54) Such molecule was presented as a prototype of that new class of psychotropic drugs. (54,55,56,57) Using the properties that were attributed to piracetam, Giurgea listed the main characteristics of a nootropic drug: (a) enhancement of learning and memory; (b) greater resistance to conditions impairing learning skills (such as electroconvulsive shocks and cerebral hypoxia); (c) protection of the brain against harmful chemical or physical agents; (d) increased efficacy of control mechanisms involved in the brain tone, at a cortical and subcortical level; (e) larger flow of information between the two brain hemispheres; (f) absence of pharmacological effects typical of other psychotropic drugs, as well as a low incidence of side effects and extremely low toxicity. (55,56,58) That way, the use of piracetam was considered to treat memory loss, and mild and moderate dementia, both related to ageing. ...
... (54,55,56,57) Using the properties that were attributed to piracetam, Giurgea listed the main characteristics of a nootropic drug: (a) enhancement of learning and memory; (b) greater resistance to conditions impairing learning skills (such as electroconvulsive shocks and cerebral hypoxia); (c) protection of the brain against harmful chemical or physical agents; (d) increased efficacy of control mechanisms involved in the brain tone, at a cortical and subcortical level; (e) larger flow of information between the two brain hemispheres; (f) absence of pharmacological effects typical of other psychotropic drugs, as well as a low incidence of side effects and extremely low toxicity. (55,56,58) That way, the use of piracetam was considered to treat memory loss, and mild and moderate dementia, both related to ageing. (55,56,58) As the effects of piracetam and of the structural analogues as of today synthesized have not yet been accepted and explained with clarity by contemporary pharmacology, that substance and the group of nootropic drugs are hardly found in pharmacology manuals. ...
... (55,56,58) That way, the use of piracetam was considered to treat memory loss, and mild and moderate dementia, both related to ageing. (55,56,58) As the effects of piracetam and of the structural analogues as of today synthesized have not yet been accepted and explained with clarity by contemporary pharmacology, that substance and the group of nootropic drugs are hardly found in pharmacology manuals. When they are included, they are described with little credibility as to their verified effects in humans. ...
By observing the processes of (bio)medicalization and pharmaceuticalization of society, this article addresses drugs that have been used by healthy individuals to increase cognitive dimensions such as alertness, memory, and concentration. The use of so-called “smart drugs” or “nootropics” has spread among young people, aided by the internet. The circulation of information about such drugs are analyzed using a Brazilian blog called “Cérebro Turbinado,” through publications available for public access between 2015 and 2017. The study adopts theoretical and methodological frameworks of the social sciences, including an anthropological perspective. Documental research was conducted on the internet, specifically with scientific dissemination materials and the material available from the aforementioned blog. The results show that the blog acts as a medium for spreading biomedical knowledge among the lay public and indicates the production of new forms of subjectivity by revealing the meanings attributed to these substances in socialization processes.
KEYWORDS:
Medicalization; Internet; Nootropic Agents; Biomedical Enhancement; Brazil
... Nootropic drugs, also known as cognitive enhancers, neuroenhancers or only recently 'smart drugs' (Cakic, 2009), were initially designed to be used in the treatment of gerontopsychiatric patients, as their main property is memory improvement (Giurgea, 1982(Giurgea, , 1973McDaniel et al., 2002;Nicholson, 1990). Nowadays, however, this name is more recognisable as the term indicating substances which enhance cognitive brain functions, such as memory, attention and concentration in healthy individuals (Giurgea, 1982;Nicholson, 1990). ...
... Nootropic drugs, also known as cognitive enhancers, neuroenhancers or only recently 'smart drugs' (Cakic, 2009), were initially designed to be used in the treatment of gerontopsychiatric patients, as their main property is memory improvement (Giurgea, 1982(Giurgea, , 1973McDaniel et al., 2002;Nicholson, 1990). Nowadays, however, this name is more recognisable as the term indicating substances which enhance cognitive brain functions, such as memory, attention and concentration in healthy individuals (Giurgea, 1982;Nicholson, 1990). Due to the attractive properties of these pharmaceuticals and practically no crucial human side effects, popularity currently gained their use as a non-prescriptive 'smart drugs', helpful especially in improving academic performance and better managing the stress of everyday life (Cakic, 2009;McDaniel et al., 2002). ...
... General features that were determined compound should possess to be classified as a nootropic drug were to activate brain mechanisms and hence compensate nervous activity deficits, without simultaneous inducement of subcortical, limbic or reticular response. Moreover, such compound should facilitate memory and learning while being non-toxic and safe (Giurgea, 1982(Giurgea, , 1973. ...
Pharmaceuticals which originally were designed to treat people with neurological and psychiatric conditions, e.g. Alzheimer's disease or attention deficit hyperactivity disorder (ADHD), are nowadays often misused by students as a 'brain doping' substances. These substances are known as nootropic drugs, smart drugs or cognitive enhancers, as they increase memory, attention and concentration of healthy individuals. Since they are easily available illicitly, their consumption is observed to be growing. Currently, these pharmaceuticals started gaining researchers' attention, especially since they have been recently detected in wastewater, surface water and even drinking water. This review summarises the current state of knowledge on nootropic drugs in terms of their population use trends and ethics, occurrence in the environment and detection techniques, toxicity and removal methods, in example of methylphenidate, modafinil and piracetam - three most popular nootropics. It points out that the main sources of knowledge on cognitive enhancers illicit use are often inconsistent questionnaires, which are not supported by wastewater analysis to become more veracious. Simultaneously, the studies concerning toxicity and removal methods of nootropic drugs are still limited and in many cases environmentally irrelevant. Although the prescription rules has been subjected to more strict control in developed countries, regulatory frameworks with regard to their ecosystem occurrence are still lacking and should be introduced. Moreover, the use of environmentally relevant concentrations in toxicity studies should be a standard, leading to proper ecotoxicity risk assessment. Based on this review, it is recommended to routinely monitor nootropics and their metabolites in waste- and surface waters.
... Piracetam is widely used in cognitive disorders and acts as nootropic drug especially in aged humans [31,32] but which key step at cellular level is involved in its neuroprotective action is yet not known. Reports have indicated that the efficacy of piracetam in experimental animals and humans is usually associated with conditions of distressed cellular energy supply that has been observed during aging and various hypoxic conditions [6,10,11,34,35] . ...
... Available reports suggest that mechanism of action of piracetam might associate with biochemical deficits typical of the senescent brain. At the subcellular level, effect of piracetam on membrane fluidity is demonstrated for membranes of brain mitochondria [31] . Beneficial effect of piracetam on the fluidity of aged membranes are observed which might lead to enhanced mitochondrial function as piracetam induced improved glucose uptake and utilization as well as ATP production is reported in neurons [36][37][38][39] . ...
... Piracetam (2-oxo-1-Pyrrolidineacetamid) ist ein medizinisch therapeutischer Wirkstoff aus der Gruppe der Nootropika, welches in den 80er Jahren entwickelt wurde (Giurgea, 1982 Patienten mit sporadischer AD nachgewiesen werden (Eckert et al., 1999), wobei in der Maus ebenfalls eine Verbesserung der Membranfluidität synaptosomaler und mitochondrialer Membranen beobachtet werden konnte . Des ...
... Piracetam wird nach oraler Gabe rasch und vollständig resorbiert, wobei die relative systemische Bioverfügbarkeit 100% beträgt. Hierbei ist Piracetam das erste Nootropikum (Giurgea, 1982) (Enderby et al., 1994;Dedeyn et al., 1996;Orgogozo, 1999;Therot and Orgogozo, 2000). ...
... 195,196 This attention to the predictivity of models was so high that in many cases, drug hunters used themselves as models and selfexperimented with molecules, exemplified by lidocaine, 197 amphetamine, 198 cromolyn, 199 bisacodyl, 200 ingenol mebutate, 201 and bremelanotide. 202 The drugs discovered based on serendipity and sagaciously observing nonhuman or ex vivo phenotypes can also be considered to be indebted to this attention toward predictive models, including bacitracin, 203,204 ticlopidine, 205 valproic acid, 206 warfarin, 207 meprobamate, 208 vinca alkaloids, 209 dipyridamole, 210 diazoxide, 211 cisplatin, 212,213 etomidate, 103 naftifine, 214 glatiramer acetate, 215,216 imiquimod, 217,218 thiazolidinediones, 219,220 levetiracetam and piracetam, 221 and dapagliflozin and empagliflozin. 222 Such serendipitous discoveries would be impossible in target-based drug discovery's biochemical affinity assays where the output is merely the affinity of a molecule for a specific protein. ...
Target-based drug discovery is the dominant paradigm of drug discovery; however, a comprehensive evaluation of its real-world efficiency is lacking. Here, a manual systematic review of about 32000 articles and patents dating back to 150 years ago demonstrates its apparent inefficiency. Analyzing the origins of all approved drugs reveals that, despite several decades of dominance, only 9.4% of small-molecule drugs have been discovered through "target-based" assays. Moreover, the therapeutic effects of even this minimal share cannot be solely attributed and reduced to their purported targets, as they depend on numerous off-target mechanisms unconsciously incorporated by phenotypic observations. The data suggest that reductionist target-based drug discovery may be a cause of the productivity crisis in drug discovery. An evidence-based approach to enhance efficiency seems to be prioritizing, in selecting and optimizing molecules, higher-level phenotypic observations that are closer to the sought-after therapeutic effects using tools like artificial intelligence and machine learning.
... O conceito original de "fármacos nootrópicos" foi sugerido em analogia à palavra "psicotrópico", pelo romeno Corneliu E. Giurgea, então chefe do Departamento de Neurofarmacologia da multinacional farmacêutica belga Union Chimique Belgue (UCB) 3 . Entre as características originalmente definidas para o perfil de um nootrópico, ressaltaram-se, principalmente, a ausência de efeitos farmacológicos comuns a outros psicotrópicos, assim como a baixa incidência de efeitos colaterais e a toxicidade extremamente baixa (GIURGEA, 1973;1982). Apesar de o conceito original tentar diferenciar os nootrópicos dos psicotrópicos conhecidos até então, sua recente ressignificação tem sido incorporada ao senso comum como sinônimo de aprimorador cognitivo. ...
Em incursão etnográfica pela internet, seguindo as pistas da divulgação científica e comercial de substâncias nootrópicas nas redes sociais (Facebook, Instagram, YouTube), discute-se o estatuto de tais substâncias, as quais compreendem ampla gama de produtos que escapam à regulação sanitária oficial, e a ressignificação do aprimoramento cognitivo farmacológico que elas promovem. Consideradas seguras e isentas de efeitos colaterais por seus propagadores, elas são indicadas e vendidas para potencializarem o aprimoramento cognitivo e a maximização da produtividade humana. Cria-se um humano otimizado. A interação entre o público leigo, interessado nas substâncias nootrópicas anunciadas e seus supostos efeitos, e os especialistas que as recomendam enseja novas biossocialidades, consagrando a lógica capitalista das tecnologias biomédicas e seus efeitos políticos e socioeconômicos em contextos de acirrada concorrência profissional e acadêmica.
... But the reality is that most of the phenotype-based drugs originated from consciously emphasizing and using highly predictive phenotypic models (about 700 drugs including most of the drugs in these categories: observing non-human or ex vivo phenotypes, mechanism of action-informed phenotypic observations, and observing phenotypic effects of endogenous molecules). This is especially evident in the discovery origins of many drugs such as isoproterenol 205 264 , dapagliflozin and empagliflozin 265 , can also be considered to be indebted to this attention toward predictive models. Such sagacious discoveries are impossible in target-based drug discovery's biochemical affinity assays whose only output is the affinity of molecules toward a single protein. ...
Target-based drug discovery is the dominant paradigm of drug discovery; however, a comprehensive evaluation of its real-world efficiency is lacking. Here, a manual systematic review of about 32000 articles and patents dating back to 150 years ago demonstrates its apparent inefficiency. Analyzing the origins of all approved drugs reveals that, despite several decades of dominance, only 9.4% of small-molecule drugs have been discovered through “target-based” assays. Moreover, the therapeutic effects of even this minimal share cannot be solely attributed and reduced to their purported targets, as they depend on numerous off-target mechanisms unconsciously incorporated by phenotypic observations. The data suggest that reductionist target-based drug discovery may be a cause of the productivity crisis in drug discovery. An evidence-based approach to enhance efficiency seems to be prioritizing, in selecting and optimizing molecules, higher-level phenotypic observations that are closer to the sought-after therapeutic effects using tools like artificial intelligence and machine learning.
... Caffeine being a commonly used supplement is a well-established ergogenic aid with multiple studies demonstrating enhanced performance through a wide range of capacities through various mechanisms via increased reaction time, attention, and information processing [1][2][3] . Nootropic (known for higher integrative brain mechanisms) effects have been related to A1 adenosine receptor antagonism in the hippocampus and cortex [3][4][5] . However, these benefits have enabled abusive caffeine supplementation patterns in athletes and non-athletes alike via pre-workout, energy drinks, and coffee consumption 2 . ...
Theacrine supplementation has begun recent investigation aimed to increase athletic performance. Although existing literature has examined theacrine's potential to increase physical and cognitive performance via adenosine receptor inhibition alongside its promotion of overall health and slight cognitive enhancement. Therefore, theacrine ostensibly exists as a caffeine substitute for attenuating both physical and mental fatigue. This article aims to (a) demonstrate the structural/mechanistic similarities of caffeine & theacrine, (b) showcase their existing performance roles, and (c) establish the need for future investigations on theacrine as a potential ergogenic aid in physically active populations to both prophylactically prevent fatigue and augment performance.
... In addition, Kennedy et al. (2013) found that cocaine-induced plasticity changes can be blocked by the inhibition of class I HDACs [32]. Clinical studies have revealed that the "nootropic" drug piracetam (2-oxo-1-pyrrolidine acetamide), a cyclic derivative of the neurotransmitter γaminobutyric acid (GABA), can modulate cognitive function without causing sedation or stimulation [33,34]. Piracetam is used as a treatment for Alzheimer's disease, dementia, memory dysfunction, alcoholism and brain injury [35]. ...
Illicit drugs are known to affect central nervous system (CNS). Majorly psychostimulants such as cocaine, methamphetamine (METH) and opioids such as morphine are known to induce epigenetic changes of histone modifications and chromatin remodeling which are mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). Aberrant changes in histone acetylation-deacetylation process further exacerbate dysregulation of gene expression and protein modification which has been linked with neuronal impairments including memory formation and synaptic plasticity. In CNS, astrocytes play a pivotal role in cellular homeostasis. However, the impact of psychostimulants and opioid mediated epigenetic changes of HAT/HADCs in astrocytes has not yet been fully elucidated. Therefore, we have investigated the effects of the psychostimulants and opioid on the acetylation-regulating enzymes- HAT and HDACs role in astrocytes. In this study, Class I and II HDACs and HATs gene expression, protein changes and global level changes of acetylation of H3 histones at specific lysines were analyzed. In addition, we have explored the neuroprotective “nootropic” drug piracetam were exposed with or without psychostimulants and opioid in the human primary astrocytes. Results revealed that psychostimulants and opioid upregulated HDAC1, HDAC4 and p300 expression, while HDAC5 and GCN5 expression were downregulated. These effects were reversed by piracetam coexposure. Psychostimulants and opioid exposure upregulated global acetylation levels of all H3Ks, except H3K14. These results suggest that psychostimulants and opioids differentially influence HATs and HDACs.
... The term 'nootropic' was coined by Corneliu E.Giurgea (1972). See alsoGiurgea (1982).Ramon Llull Journal_11.indd 285 4/5/20 13:58 ...
Tackling climate change is one of the most demanding challenges of humanity in the 21 st century. Still, the efforts to mitigate the current environmental crisis do not seem enough to deal with the increased existential risks for the human and other species. Persson and Savulescu have proposed that our evolutionarily forged moral psychology is one of the impediments to facing as enormous a problem as global warming. They suggested that if we want to address properly some of the most pressing problems that cause catastrophic harm to our existence, we should enhance our moral behavior by biomedical means. The objective of this paper is, precisely, to reflect on whether a Moral Bio-Enhancement (henceforth MBE) program would be a viable option to confront the climate emergency. To meet this goal, I will propose the Ultimate Mos-tropic (hereafter UM) thought experiment, a hypothetical situation where we have already discovered the UM, an available, safe (without any del-eterious secondary effects), extremely cheap and effective pill to enhance our cognitive, affective and motivational abilities related to morality. After briefly presenting the main argument of Persson and Savulescu regarding MBE and climate change, I will point out some of the difficulties that make MBE a daunting but exciting philosophical and scientific debate. In order to overcome these complications, I will describe the UM thought experiment, which involves two scenarios of the MBE program: (a) the state-driven, compulsory and universal enterprise, and (b) the initiative of voluntary individuals. I will show that the shortcomings of MBE programs through the UM in both scenarios make Persson and Ramon Llull Journal_11.indd 277 4/5/20 13:57 278 RAMON LLULL JOURNAL OF APPLIED ETHICS 2020. ISSUE 11 PP. 277-303 Savulescu's proposal a not appealing pathway to mitigate climate change. In the final section, I will suggest that an inaccurate attribution of responsibilities underlies their proposal and that the collective inaction problem should be redirected primarily through a reinforcement of the political nature of the solutions.
... De este modo, decidió crear una nueva categoría, la de los nootrópicos. Las características principales de estos fármacos serían: mejorar las capacidades de aprendizaje, facilitar la transmisión de información entre hemisferios cerebrales, poseer capacidades neuroprotectoras, carecer de acusados efectos secundarios (presentes usualmente en otros fármacos) y no generar adicción (Giurgea, 1982). ...
La superación de las capacidades cognitivas humanas conforma uno de los ejes centrales de las propuestas transhumanistas. A mitad de camino entre lo actual y lo posible, aparece en las últimas décadas otra forma de aproximarse a la superación de la mente humana: las smart drugs —también conocidas como cognitive enhancers o nootrópicos—, psicofármacos que prometen una mejora de la cognición, la memoria, la inteligencia, la atención, la concentración... Estos fármacos son actualmente empleados en el ámbito terapéutico, pero son muchos quienes consideran que las barreras entre terapia y mejora humana comienzan a desdibujarse. Este trabajo presenta tres smart drugs —metilfenidato, modafinilo y piracetam— y reflexiona sobre los límites entre terapia y mejora, poniendo especial énfasis en los problemas axiológicos que comportan.
... Broad-spectrum plant-derived natural compounds for increasing neuro-functioningsuch as Ginseng, Passion Flower, Hippophae and coffee -have been a full part of medical practice in various cultures for centuries. The effectiveness of these neuro-enhancing herbs in improving concentration and alertness was confirmed from a scientific perspective many years ago, and they have come to be collectively known as "adaptogens" (Brekhman and Dardymov 1969 (Giurgea 1982). By advocating that: ...
... A large-scale, 12-week trial of high-dose piracetam showed that piracetam caused no adverse effects when compared to a placebo group. Several studies reported that piracetam was well tolerated [4][5][6]. ...
Background: Corpus callosum is a large nerve tract consisting of a flat bundle of commissural fibers that runs below the brain cerebral cortex. It connects the left and right cerebral hemispheres. Absence of the corpus callosum because of failure of development is a rare congenital defect called “Agenesis of the corpus callosum”.
Patients and Methods: Two Iraqi infants with non-syndromic agenesis of the corpus callosum were observed. One infant had the isolated type and the second infant had agenesis of the corpus callosum associated with colpocephaly.
Both infants had the clinical features of the syndrome resulting from the associated failure of neuronal migration including hypotonia with poor head control, no response to voice, not recognizing faces, and they didn’t show any eye contact. They have never smiled and had poor spontaneous movements.
The patient with colpocephaly was a girl and, she was treated with courses of intramuscular piracetam and cerebrolysin for three months with aim of improving brain functions and accelerating her development. The second patient was a boy and he didn’t receive any specific therapy.
Results: Treatment was not associated with any side effects, and after three months of treatment, the patient experienced improvements in feeding, muscle tone, alertness and response to voice, and movements.The untreated patient didn’t show any obvious improvement despite he didn’t have colpocephaly.
Conclusion: Further studies enrolling a larger number of patients are recommended.
... 16,17 These are claimed to improve the higher telencephalic integrative activities in the brain and restore deficient higher nervous system activity without affecting subcortical functions. 18 Unlike other psychotropic drugs, nootropics do not cause sedation or stimulation and are completely devoid of toxic effects, even when administered in very high doses. Piracetam has been reported to possess cytoprotective, antioxidant, antihypoxic and microcirculation protective effects. ...
Valproic acid (VPA) is an antiepileptic drug which is widely used in humans and is a well known teratogenic agent when used during pregnancy. Piracetam is a nootropic or cognitive enhancer drug used to treat cognitive impairment in aging, brain injuries as well as dementia. In the present study, these two drugs VPA and Piracetam were administered orally to Swiss albino mice in the doses of400 mg/kg and 800 mg/kg body weight respectively from gestational day (GD) 6-11 in order to see the protective effect of Piracetam against VPA induced teratogenesis. The fetuses were collected on GD 18 after uterotomy and observed for gross malformations if any. In VPA treated group the malformations observed were exencephaly, cranioschisis, limb and tail defects, haemorrhage, resorptions and retardation. No such anomalies were observed in control and Piracetam treated groups. However,in VPA+ Piracetam treated group some resorptions and growth retardation were noted. This group showed highly significant (p < 0.001) protection against the teratogenic effects of VPA treated group though the developmental parameters were significantly reduced (p < 0.001) in comparison to those of group I (control) and group III (receiving piracetam). These findings suggest that Piracetam, if given in higher doses might protect the development in utero against the teratogenic effects of VPA.
... Drugs such as nootropic, methylphenidate, and modafinil can enhance cognitive abilities, including one's attention, concentration, and vigilance. They improve the brain's oxygen supply by stimulating nerve growth or altering the organ's neurochemicals [25,66,67]. Nootropics, in particular, have been shown to increase the concentration, alertness, and memory potential, while also potentiating the cognitive function in healthy subjects [45,68,69]. ...
This paper presents the first comprehensive review on vigilance enhancement using both conventional and unconventional means, and further discusses the resulting contradictory findings. It highlights the key differences observed between the research findings and argues that variations of the experimental protocol could be a significant contributing factor towards such contradictory results. Furthermore, the paper reveals the effectiveness of unconventional means of enhancement in significant reduction of vigilance decrement compared to conventional means. Meanwhile, a discussion on the challenges of enhancement techniques is presented, with several suggested recommendations and alternative strategies to maintain an adequate level of vigilance for the task at hand. Additionally, this review provides evidence in support of the use of unconventional means of enhancement on vigilance studies, regardless of their practical challenges.
... The subreddit's wiki 3 (i.e., user-created encyclopedia) lists approximately 200 substances described as "commonly discussed". Among these are amphetamines and psychedelics, which are explicitly excluded from the nootropics category by Giurgea (1982), a fact also acknowledged in the wiki. At the time of writing, Nootropics has 125,627 'subscribers', that is, Reddit users receiving updates about new posts and comments. ...
Aims
The use of substances for cognitive enhancement has become a relatively well-studied phenomenon in recent years. However, few studies deal with the negative and unintended consequences of such practices. This article uses two data sets to explore and discuss the doubt and negative consequences that affect people using substances in the pursuit of enhancing cognition.
Methods
Data for the study are drawn from an online discussion forum on substances for enhancement and from ethnographic fieldwork carried out among university students in New York City. Taking a quali-quantitative approach, we combine digital text analytic tools with qualitative analysis and readings.
Findings
Using prescription stimulants and other substances for cognitive enhancement generates considerable uncertainty in terms of unclear effects, varying practices and ambivalent ethics. While the negative effects are not something easily discussed in person, references to them are very common in the online discussion forum.
Conclusions
People who use substances for enhancement have developed a ‘folk pharmacology’ that seems to play an important role in how they perceive the negative effects. This may make people who engage in these kinds of enhancement practices less able to make informed choices about their use of these substances.
... Broad-spectrum plant-derived natural compounds for increasing neuro-functioningsuch as Ginseng, Passion Flower, Hippophae and coffee -have been a full part of medical practice in various cultures for centuries. The effectiveness of these neuro-enhancing herbs in improving concentration and alertness was confirmed from a scientific perspective many years ago, and they have come to be collectively known as "adaptogens" (Brekhman and Dardymov 1969 (Giurgea 1982). By advocating that: ...
With the increasing number and performance of instruments related to brain imaging technologies (e.g., EEG, fMRI), there is a growing risk that the protection of one's private life and personal information will be challenged. » « Further tangible future applications include adapting advertisements to consumers' preferences after reading their minds and gaining access to and taking advantage of health data and intimate thoughts.»
... Previously we have reported that piracetam offered protection against oxidative DNA damage in peripheral blood leukocytes . It showed the membrane fluidity effect of piracetam at the sub-cellular level for membranes of brain mitochondria (Giurgea et al. 1982). It also showed the protective effect towards mitochondrial function (Keil et al. 2006), which gets altered in most of the neurological disorders. ...
Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4 mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells in region specific manner. The study is also revealing the rationale for its clinical use in cognitive impairment and other neurological diseases.
... Previously we have reported that piracetam offered protection against oxidative DNA damage in peripheral blood leukocytes . It showed the membrane fluidity effect of piracetam at the sub-cellular level for membranes of brain mitochondria (Giurgea et al. 1982). It also showed the protective effect towards mitochondrial function (Keil et al. 2006), which gets altered in most of the neurological disorders. ...
... Сле дует отметить, что на выработку и на функциональное нарушение инструментальных оборонительных реак ций невозможно прямое перенесение приемов, разра ботанных для пищевых условных рефлексов (Анохин, 1968). В связи с этим были предложены модели функ циональных нарушений УРАИ у крыс, основанные на нарушении однозначности причинно-следственных (Иноземцев, Прагина, 1989) и пространственных отно шений (Иноземцев, Прагина, 1992) в эксперименталь ной среде, рекомендованные в качестве дополнительных методов исследования ноотропной и анксиолитической активности (Воронина, Середенин, 2000; Воронина, Островская, 2000Giurgea 1982; Hoof, 1980), но к настоящему времени стали известны работы, в которых этот эффект не наблюдался (Рахманкулова и др., 1985; Иноземцев, Прагина, 1992; Иноземцев, 1997; Островская и др., 2002; Means et al., 1980; Pohle et al., 1997) или наблюдался в зависимости от факторов, не всегда поддающихся экспериментальному контролю (Mondadori et al., 1989; Sansone, Oliverio, 1989). Это побудило экспериментаторов к применению воздей ствий, нарушающих обучение и память, таких, как максимальный электрошок, скополамин, ишемия, фронтальная лобэктомия (Воронина, Островская, 2000), длительное стрессирование животных с помощью элек трического тока (Cavoy et al, 1988), а также используе мых в данной работе функциональных нарушений выработанных реакций, Сбой вызвал глубокое нарушение выработанного навыка у контрольных животных во всех сериях опы тов (рис. ...
... Because it does not interact with any specific known target structure, the most probable explanation seems to be its binding to the polar headgroups of membrane phospholipids [28,29]. Piracetam offers beneficial effects during aging or pathological conditions such as hypoxia, glucose deprivation, injuries, or free radical damage [14,28] and it must be noted that all these conditions, even if other deficits are also present, are associated with the vicious cycle involving energy (ATP) deficit, oxidative stress, and mitochondrial dysfunction consequently leading to cell death. ...
The present study was performed to investigate the involvement of mitochondrion - specific endonuclease G in piracetam (P) induced protective mechanisms. Studies have showed the antiapoptotic effect of piracetam but still there are some unfold enigma for the mechanism of action of piracetam. To assess the involvement of endonuclease G in piracetam induced protective effects, the astrocyte glial cells were treated with Lipopolysaccharide (LPS) / LPS+P. LPS treatment caused significantly decreased viability, mitochondrial activity, oxidative stress, chromatin condensation and DNA fragmentation which were attenuated with piracetam co-treatment. Piracetam co-treated astrocytes showed its significant time dependent absorption as observed with high performance liquid chromatography data. Piracetam per se treated astrocytes showed the enhanced mitochondrial membrane potential (MMP) in comparison to control astrocytes. However, in LPS treated cells no significant alteration in MMP was observed in comparison to control cells. Protein and mRNA levels of terminal executor of caspase mediated pathway, caspase-3 did not alter significantly in LPS or LPS+P treated astrocytes whereas endonuclease G was significantly translocated to nucleus in LPS treated astrocytes. Piracetam co-treatment attenuated the LPS induced endonuclease G translocation. In conclusion study indicates that LPS treatment to astrocytes caused decreased viability, oxidative stress, mitochondrial dysfunction, chromatin condensation, DNA damage and translocation of endonuclease G to nucleus which was inhibited with piracetam co-treatment and confirming the mitochondrion-specific endonuclease G as one of the factor involved in piracetam induced protective mechanisms.
Nootropics, also known as cognitive enhancers or "smart drugs," have garnered increasing attention in the sports world as potential aids for enhancing mental performance. This thematic paper explores the intersection of nootropics and sports, delving into their potential benets and ethical considerations. While the use of these substances in sports raises intriguing possibilities for optimizing cognitive function during training and competition, it also presents signicant challenges in terms of safety, fairness, and the potential for abuse. This paper aims to provide an indepth analysis of the implications of incorporating nootropics in sports and encourages a balanced approach to this complex and evolving subject.
Mimicking nature's efficiency and sustainability in organic chemistry is a major goal for future chemists; redox reactions are a key element in a variety of fields ranging from synthesis and catalysis to materials chemistry and analytical applications. Sustainability is increasingly becoming a consideration in synthesis and functional chemistry and an essential element for the next generation of chemistry in academia and industry. This book represents a compilation of the latest advancements in functional redox chemistry and demonstrates its importance in achieving a more sustainable future. This book is an ideal companion for any postgraduate students or researchers interested in sustainability in academia and industry.
Rotenone is a broadly used organic pesticide with neurotoxicity as a serious side effect for non-target organisms. The inhibition of mitochondrial complex I is the principal mechanism of rotenone toxicity that leads to oxidative stress, apoptosis, and decreased autophagy. Several chemical compounds have been demonstrated to exhibit antioxidant, antiapoptotic, and autophagy enhancement in both in vitro and in vivo studies. Some chemical agents can ameliorate rotenone-induced neurotoxicity through their antioxidant, anti-inflammatory, and anti-apoptotic properties. They also inhibit the accumulation of α-synuclein, control dopamine release, affect ion channels, and induce autophagy. Clinical trials are essential to reinforce the effectiveness of any chemical in managing patients with rotenone neurotoxicity.
Piracetam is generally utilized as a nootropic drug, which is normally used in the treatment of CNS disorders. Piracetam is a cyclic compound and a derivative of γ-aminobutyric acid and improves learning, memory, brain metabolism, and ability. This drug belongs to the racetams group with the chemical name 2-oxo-1-pyrrolidine acetamide. The emphasis of this review article is to highlight different biological activities associated with piracetam and also some of its synthetic methodologies. Promising effects have been achieved in the management and treatment of several diseases for example alcoholism, Raynaud’s phenomenon, deep vein thrombosis and brain injury.
Substance abuse affects the central nervous system (CNS) and remains a global health problem. Psychostimulants, such as cocaine and methamphetamine (METH), and opioids affect neuronal function and lead to behavioral impairments via epigenetic modification. Epigenetic changes occur via classical pathways, especially the class III histone deacetylase (HDAC)-sirtuin (SIRT) family, that act as cellular sensors to regulate energy homeostasis and coordinate cellular responses to maintain genome integrity. However, SIRT family (1–7)-associated neurodegeneration has not been elucidated in the context of energy metabolism. The present study examined the effects of psychostimulants, such as cocaine and METH, and opioids, such as morphine, on SIRT family (1–7) [class I, II, III and IV] expression and cellular translocation-mediated dysfunction in astrocytes and microglial cells. The “nootropic” drug piracetam played a preventative role against psychostimulant- and opioid-induced SIRT (1–7) expression in astrocytes. These results indicate that cocaine, METH, and morphine affected deacetylation and cellular function, and these changes were prevented by piracetam in astrocytes.
Pharmacological intervention for the augmentation of brain function in healthy individuals and for recovery after neurological conditions has reached new horizons. The advent of neuro-technologies, such as advanced functional imaging techniques and neurostimulation methods, offers valuable new data about the multiple levels of organization within the brain, uncovering crucial insights about the dynamic cross talk between cerebral networks. From nutritional components and traditional natural remedies to synthetic psychostimulants or multimodal agents, a wide range of interventions are currently used to enhance brain function. Of these, some have raised questions concerning safety, efficacy, and overall effectiveness. In response to increasing demands for cognitive performance or to an internal insult, the nervous system relies on the endogenous defense activity: a process of continuous modulation of neurobiological processes of neurotrophicity, neuroprotection, neuroplasticity, and neurogenesis. In this chapter, several pharmacological brain enhancers are reviewed to assess their capacity to support the brain’s anticorrelated endogenous defense mechanisms.
Astrocytes are the primary regulator of energy metabolism in the central nervous system (CNS), and impairment of astrocyte's energy resource may trigger neurodegeneration. HIV infections and cocaine use are known to alter epigenetic modification, including miRNAs, which can target gene expression post-transcriptionally. However, miRNA-mediated astrocyte energy metabolism has not been delineated in HIV infection and cocaine abuse. Using next-generation sequencing (NGS), we identified a total of 1900 miRNAs, 64 were upregulated and 68 miRNAs were downregulated in the astrocytes by HIV-1 Tat with cocaine exposure. Moreover, miR-4727-3p, miR-5189-5p, miR-5090, and miR-6810-5p expressions were significantly impacted, and their gene targets were identified as VAMP2, NFIB, PPM1H, MEIS1, and PSD93 through the bioinformatic approach. In addition, the astrocytes treated with the nootropic drug piracetam protects these miRNAs. These findings provide evidence that the miRNAs in the astrocytes may be a potential biomarker and therapeutic target for HIV and cocaine abuse-induced neurodegeneration.
Resumo O consumo de medicamentos para aprimorar processos mentais, como memória, concentração e estado de alerta, tem se expandido. As chamadas smart drugs e fármacos nootrópicos são utilizados na expectativa de obter melhor desempenho em tarefas profissionais e acadêmicas. Este artigo analisa a difusão do uso de medicamentos para aprimoramento cognitivo, a partir de um blog brasileiro chamado Cérebro Turbinado, com ênfase na discussão da categoria “nootrópicos”. A metodologia adotada foi a pesquisa socioantropológica documental, baseada em materiais de divulgação científica que integram o conteúdo do blog, criado em 2015 por um estudante de medicina de uma universidade pública. O blog apresenta os nootrópicos como opções mais acessíveis, seguras e igualmente eficazes em comparação com os medicamentos psicotrópicos utilizados como smart drugs. Editor e leitores produzem um saber coletivo para otimizar o desempenho cerebral. As experiências pessoais evidenciam a maneira como os indivíduos interpretam seus estados corporais e os relacionam com os medicamentos. Na esteira dos processos de farmacologização da sociedade, a produção de modos de subjetividade baseadas em uma concepção individualista dos processos de saúde/doença/incapacidade, apoiada na compreensão neuromolecular do cérebro, fundamenta-se no compartilhamento de práticas e conhecimentos sobre tais substâncias.
Nootropic compounds are a group of pharmacologically active pyrrolidones. These molecules, which enhance cognition properties and possess a large prescription field, are particularly interesting synthetic targets for the pharmaceutical industry. In this Article, we disclose an effective and environmentally friendly pyrrolidinone synthesis using electrosynthesis. The newly developed methodology includes a Kolbe decarboxylation, followed by an intramolecular radical cyclization and a radical-radical cross-coupling.
Brain's neurodegenerative diseases are one of the most actual problems of neurology and neurobiology. The lack of the modern methods of treating this diseases stimulates to develop new effective approaches based on neuronal and glial cells, which requires studying the signaling mechanisms of neural differentiation. This review considers the key mechanisms and substances involved in the formation of the neuroepithelium in vivo, as well as for obtaining the neural stem cells from iPSCs and its further differentiation in various types of neuronal and glial cells in vitro.
A number of alternative approaches can affect cognitive function. Presently, there is no evidence that neurofeedback can be used to enhance intelligence in healthy individuals; however, it presents a promising tool for improving specific cognitive processes, such as attention and memory. The development of new methods that enable self-regulation of functional connectivity between regions of interest may provide a platform for enhancing performance on tests of intelligence. Research suggests that adhering to a healthy lifestyle, which involves a balanced diet, regular exercise, and stress management, has neuroprotective effects. Moderate intensity physical activity seems to be one of the best methods currently available to promote brain health, and counteract age-related cognitive decline. While there is substantial evidence for meditation-related reduction in psychological stress and anxiety, and some evidence for improvement in various components of attention, no conclusions can be drawn with respect to its effect on measures of intelligence. Finally, nutrition plays an important role in the child’s intellectual development; multiple micronutrient supplementation to infants and children who have micronutrient deficiencies can improve fluid intelligence. Certain dietary supplements may also help preserve cognitive function in the elderly. The use of drugs for the purpose of improving cognitive functions by healthy individuals raises several concerns with respect to medical safety and ethics. Prescription stimulants can produce short-term improvements in memory and executive function in healthy individuals; however, the long-term effects of the use of cognitive enhancers remain unknown.
All approaches to the treatment of dementia are intended primarily to improve cognitive deficits and the factors responsible for them, and secondarily to improve the accompanying “noncognitive” manifestations. Both of these types of disease manifestation are amenable to treatment by pharmacological and non-pharmacological means. In this chapter, we shall discuss the medical treatment of dementia and the social and psychological interventions that may be directed against the disease. The use of neuroleptics and antidepressants to treat disturbances accompanying dementia is discussed in Vol. 2, Part 1, Chap. 11.
Psychopharmacologists are interested in measuring psychoactive drug-induced changes in cognitive and/or psychological behavior (Hindmarch and Stonier, 1987; 1989; Hindmarch et al., 1988). The number of tests included in a test battery should be kept to a minimum to avoid identifying significant results by chance, and individual tests should be appropriate for the particular psychological function under investigation, e.g., psychomotor performance, information processing capacity (IPC)/CNS integration, and memory (Hindmarch and Wattis, 1988). It is frequently unclear what a particular test is supposed to be measuring (Adams, 1974; Lahtinen et al., 1978). Pre-experimental screening of subjects and the control of confounding variables will also increase the sensitivity of psychometric measures and facilitate the interpretation of results.
Die Behandlungsansätze zielen in erster Linie auf die kognitiven Defizite der Demenzen und deren Grundlagen und zweitens auf die „nicht kognitive“ Begleitsymptomatik. In beiden Bereichen können sowohl medikamentöse als auch nichtmedikamentöse Strategien eingesetzt werden. In unserem Beitrag befassen wir uns mit den antidementiven Pharmaka sowie mit soziopsychologischen Interventionen. Die neuroleptische und antidepressive Behandlung bei entsprechenden begleitenden Störungen wird in Kap. 11, Bd. 3 diskutiert.
Da tier- und humanexperimentell ermittelte pharmakologische und biochemische Untersuchungsergebnisse lediglich Aussagen zur Wirkung der Nootropika zulassen, muß die Bewertung der Wirksamkeit ausschließlich nach klinischen Kriterien erfolgen.
Die Leistungsfähigkeit des Zentralnervensystems wird in wesentlichem Maße von der Struktur und der Funktion der neuronalen synaptischen Konnektivität bestimmt. Störungen synaptischer Übertragungsprozesse sind von funktioneller Relevanz und beachtlicher pathogenetischer Bedeutung für neuropsychiatrische Erkrankungen. Deshalb hat die Erforschung der normalen und krankhaft veränderten synaptischen Übertragung sowie deren pharmakologische Beeinflußbarkeit seit langem besondere Aufmerksamkeit gefunden und bildet auch heute einen Schwerpunkt der neurobiologischen Forschung.
Die Entwicklung der Gerontopsychopharmakologie wurde nicht, wie das für die allgemeine Psychopharmakologie der Fall war, durch die zufällige Entdekkung klinisch eindeutig wirksamer Substanzen — wie z. B. des antipsychotisch wirksamen Chlorpromazins im Jahre 1952 durch Delay u. Denniker — eingeleitet. Hinzukommt, daß die systematische wissenschaftliche Untersuchung dieser Substanzen ihrerseits eine auf pharmakologischen Hinweisen beruhende biologische Ursachenforschung der Depression und Schizophrenie induziert hat. Da ähnliche „glückliche“ Entdeckungen bisher der Gerontopsychopharmakologie nicht zuteil wurden, sind in diesem Bereich andere Strategien zur Entwicklung einer rationalen Gerontopharmakotherapie erforderlich. Eine sich anbietende Chance liegt vor allem in der Intensivierung der Erforschung der biochemischen Grundlagen der morphologischen Veränderungen des sog. physiologischen Alterungsprozesses sowie der degenerativ bzw. vaskulär bedingten Abbauerkrankungen. Das Fehlen pharmakologischer Wegweiser im oben genannten Sinne muß dabei durch die auf der Basis der Grundlagenforschung entwikkelten hypothetischen pharmakologischen Modelle ersetzt werden. Wenn auch bisher die Mehrzahl der zu prüfenden hypothetischen pharmakologischen Modelle im Endergebnis nicht bestätigt werden konnten, so liegt ihr Wert trotzdem in der Etablierung einer beginnenden und naturgemäß noch sehr simplifizierenden rationalen gerontopharmakologischen Forschung. Diese Forschungsansätze einer rationalen Gerontopharmakologie sollten in Zukunft stärker gefördert und unterstützt werden.
Eine der vielen Veränderungen, die in unserem zentralen Nervensystem im Verlaufe des normalen Alterns nachweisbar sind, ist eine Abnahme der Dichte verschiedener Neurotransmitterrezeptoren. Eine Zusammenfassung solcher altersbedingter Rezeptorabnahmen im Zentralnervensystem von Ratte und Maus ist in Tabelle 1 dargestellt. Die Frage, inwieweit sich diese Veränderungen der Neurotransmitterrezeptoren mit zunehmendem Alter auch in entsprechenden Veränderungen der Rezeptoreffektorsysteme niederschlagen, ist noch nicht für alle dieser Rezeptoren untersucht. Erste Evidenzen für eine Abnahme der rezeptorgekoppelten Aktivierung der Adenylatzyklase existieren in der Ratte für den Dopaminrezeptor, den Histaminrezeptor und den β-adrenergen Rezeptor (MAKMAN et al. 1979; PALM U. WIEMER 1982).
The behavioral experiments using a passive avoidance learning model showed that the new cognition-enhancing acyl - prolyn containing dipeptide GVS-111 promotes recovery of the test performance in animals with a long-term memory deficit caused by the M-cholinolytic scopolamine (1 mg/kg/day scopolamine for 20 days, followed by 0.5 mg/kg/day GVS-111 for 10 days). At the same time, GVS-111 increased the duration of tremor induced by the M-cholinomimetic arecoline. The results of electrophysicological experiments showed that GVS-111 in a concentration range from 10-11 to 10-9 M increased amplitude of the neural response to acetylcholine (Ach) microappications in 75% of the isolated neurons of Helix Pomatum and produced a predominantly facilitating effect upon the endoneuronal pacemaker activity. The effect of GVS-111 upon the Ach response in a part of neurons was attenuated or even blocked by scopolamine and in the other neurons - by the N-cholinolytic d-tubocurarine. This fact indicates that both muscarinic and nicotinic receptors are involved in the mechanism of the cholino-sensitizing action of GVS-111 upon the neuronal activity.
The effect of piracetam at various doses on the behavioral and electrophysiological characteristics was studied, including the development of passive and active avoidance conditional reflexes in rats, their behavior in conflict situations, and the transcallosal evoked response (TER) in rabbit brain. In the dose range from 50 to 300 mg/kg, piracetam improved the avoidance performance of both types and produced a dose-dependent increase in the TER amplitude, but did not affect the behavior of rats in conflict situations. As the drug dose was increased to 400 - 1000 mg/kg, the positive learning influence disappeared (sometimes the effect was even negative) and the TER increase changed to decrease. In contrast, the conflict situation tests revealed pronounced anxiolytic activity of piracetam at elevated doses. Thus, the nootropic and anxiolytic effects of piracetam (and, probably, of the other tranquilizers as well) do not coexist and are significantly shifted relative to one another on the dose scale, being probably realized via different mechanisms.
Objective(s): Learning is defined as the acquisition of information and skills, while subsequent retention of that information is called memory. The objective of the present study was to investigate the effect of aqueous extract of Boswellia papyrifera on learning and memory paradigms in mice and rats. Materials and Methods: This study was held at the Department of Pharmacology, Faculty of Pharmacy, Kermanshah University of Medical Science, Kermanshah, Iran from September 2006 to March 2008. Male Wistar rats and male NMRI mice were randomly divided into control, B. papyrifera treated (50, 100, 150 mg/kg, p.o.), and piracetam (150 mg/kg) groups. Radial arm maze (RAM) and Morris water maze (MWM) were the screening tests used to assess the activity of B. papyrifera extract. Results: The mice treated with B. papyrifera (50, 100 and 150 mg/kg) or piracetam (150 mg/kg) showed a decrease in number of days required to learned (P< 0.05) and time taken to find food by the learned mice in radial arm maze (P< 0.01). In Morris water maze, rats treated with the above mentioned doses showed dose dependent improvement in spatial learning. Escape latency during swimming in water maze in piracetam and B. papyrifera treated animals was significantly lower (P< 0.01) than control. Swimming distance was also significantly lower (P< 0.05) in the treated groups. Conclusion: The results show facilitation of spatial learning and memory processes and thereby validate B. papyrifera traditional use of intelligence improving. The presence of alkaloids, flavonoids and saponins might be responsible for this activity of B. papyrifera.
Nootropic drugs literally mean drugs that act on the mind. The term nootropic derives from the Greek words noos (mind) and tropein (toward), and was coined in about 1972 by Corneliu Giurgea to categorize the new drug piracetam, the pharmacology of which did not fit any of the known groups of psychotropic drugs (Giurgea, 1982). And while complete agreement between pharmacologists has not yet been attained, the vast majority agree that nootropic drugs have at least the following properties in common. They improve some aspect of cognitive performance—usually learning and/or memory in animals. The improved cognitive performance is most readily (although not necessarily) seen under conditions of disturbed neural metabolism (hypoxia, intoxication, aging, trauma). The agents have very minimal or essentially no side effects even at very high doses. The agents must pass the blood-brain barrier. They have no vasoconstrictive or vasodilative actions. Skondia (1979) has proposed a somewhat longer and more mechanistic set of criteria for defining a nootropic agent. However, his mechanistic requirements make his list more controversial.
The crystal and molecular structures of the nootropic agents RU-47001 ((±) 1-(4-nitrobenzenesulphonyl)-2-oxo-5-ethoxypyrrolidine) and RU-47064 ((±) 1-(4-nitrobenzenesulphonyl)-2-oxo-5-isopropyloxypyrrolidine) have been determined by X-ray analysis and their solution conformation has been investigated using 1H NMR spectroscopy. The conformations of these molecules together with those of their analogues RU-35929 ((±) 1-benzenesulphonyl-2-oxo-5-ethoxypyrrolidine), RU-47010 ((±) 1-(3-pyridinylsulphonyl)-2-oxo-5-ethoxypyrrolidine) and RU-35965 ((±) 1-benzenesulphonyl-2-oxo-5-isopropyloxypyrrolidine) have been deduced from semi-quantitative PM3 type theoretical calculations. The main feature of all compounds consists of a common envelope conformation with C (4) at the flap of the pyrrolidinone ring in the solid, that in solution changes into the analogous, but opposite, possible puckered conformational isomer. The 5-alkoxy groups were found rather flexible in solution. Theoretical preferred conformations about NS and SC bonds were in acceptable agreement with those of the solid state. The calculated torsional energetics suggested that 1-5 do not undergo conformational interconversion.
The title compound, C12H12N2O5, is a potential antiamnesic agent. The pyrrolidinone ring has an envelope conformation, and the central moiety is almost coplanar with the planes of the phenyl and pyrrolidinone rings. In the crystal structure, weak intermolecular C—H...O interactions link the molecules into a complex network that can be described by (X) rings (X = 16, 20 and 26) and a C(12) chain.
Despite immense advances in the treatment strategies, management of neuropathic pain remains unsatisfactory. Piracetam is a prototype of nootropic drugs, used to improve cognitive impairment. The present study was designed to investigate the effect of piracetam on peripheral neuropathic pain in rats. Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, piracetam was intraperitoneally administered for 2 weeks in doses of 50, 100 and 200 mg/kg, and pain was assessed by employing the behavioural tests for thermal hyperalgesia (hot plate and tail flick tests) and cold allodynia (acetone test). After the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of piracetam (50 mg/kg) did not have any significant effect on all the behavioural tests. Further, piracetam (100 mg/kg) also had no effect on the hot plate and tail flick tests; however it significantly decreased the paw withdrawal duration in the acetone test. Piracetam in a dose of 200 mg/kg significantly modulated neuropathic pain as observed from the increased hot plate and tail flick latencies, and decreased paw withdrawal duration (in acetone test). Therefore, the present study suggests the potential use of piracetam in the treatment of neuropathic pain, which merits further clinical investigation.
The metabolic enhancer piracetam is used in many countries to treat cognitive impairment in aging, brain injuries, as well as dementia such as AD (Alzheimer's disease). As a specific feature of piracetam, beneficial effects are usually associated with mitochondrial dysfunction. In previous studies we were able to show that piracetam enhanced ATP production, mitochondrial membrane potential as well as neurite outgrowth in cell and animal models for aging and AD. To investigate further the effects of piracetam on mitochondrial function, especially mitochondrial fission and fusion events, we decided to assess mitochondrial morphology. Human neuroblastoma cells were treated with the drug under normal conditions and under conditions imitating aging and the occurrence of ROS (reactive oxygen species) as well as in stably transfected cells with the human wild-type APP (amyloid precursor protein) gene. This AD model is characterized by expressing only 2-fold more human Aβ (amyloid β-peptide) compared with control cells and therefore representing very early stages of AD when Aβ levels gradually increase over decades. Interestingly, these cells exhibit an impaired mitochondrial function and morphology under baseline conditions. Piracetam is able to restore this impairment and shifts mitochondrial morphology back to elongated forms, whereas there is no effect in control cells. After addition of a complex I inhibitor, mitochondrial morphology is distinctly shifted to punctate forms in both cell lines. Under these conditions piracetam is able to ameliorate morphology in cells suffering from the mild Aβ load, as well as mitochondrial dynamics in control cells.
Major cognition disorder includes mental retardation, learning disabilities, amnestic syndromes, and the dementias. Many disorders and diseases of the central nervous system (CNS), which have cognitive sequelae, although they are not primarily cognitive disorders, for example, epilepsy and schizophrenia, are in the center of attraction to the researchers in the field of neuroscience. Recent clinical evidence, along with earlier laboratory studies, indicates that the cognitive defects in Alzheimer's disease, the primary cause of dementia in the elder due to loss of functioning of cholinergic neurons in the brain. This chapter briefly discusses the active research area, and then discusses the other chemotherapeutic approaches that show promise in the treatment of cognitive dysfunction. Several experiments and animal models have been in use for the sake of discussion in the chapter. Studies of the biochemical and histopathological changes in Alzheimer's patients, particularly in the cholinergic system, have opened new approaches to developing the animal models for testing hypotheses and new chemical entities. Clinical trials of amphetamine, methylphenidate, pentylenetetrazol, and pipradol have generally failed to insignificant effects upon cognition in impaired elderly subjects, although mood improvement and reduction in fatigue have been noted. It has been suggested that while vasopressin is involved in memory processes, the neuropeptides adrenocorticotropic hormone (ACTH)/melanocyte-stimulating hormones (MSH) affect motivational and attentive processes. However, studies comparing the effects of a number of neuropeptides on short-term memory in young adult primates indicated that a-MSH produced some facilitation of memory.
1.1. Nootropic drugs were proposed as a class of psychoactive drugs that selectively improve efficiency of higher telencephalic integrative activities.2.2. The main features of the nootropic profile consist of: (a) enhancement of learning acquisition; (b) resistance to impairing agents; (c) facilitation of interhemispheric transfer of information; (d) enhanced resistance to brain “aggressions”; (e) increased tonic, cortico-subcortical “control”; and (f) absence of usual pharmacological effects of neuro psychotropic drugs.3.3. The animal experimental results are thoroughly corroborated by the data obtained in clinical pharmacology and pharmacotherapeutics supporting the concept that nootropic activity is based on a functional telencephalic selectivity.4.4. The basic mechanism of action at molecular and cellular levels of nootropic drugs is not yet known. Some recent data emphasized a possible role for cerebral ATP.
Sixteen male dyslexic children were seen again when adults and matched with 14 student volunteers for a 21-day trial of piracetam. It was found, using a double-blind cross-over technique, that dyslexics significantly increased their verbal learning by 15.0% and students by 8.6% (over and above their placebo increase).
In search of a common biochemical denominator of the action of the nootropic drug 2-oxo-pyrrolidine-1-acetamide (piracetam, Normabrain, Nootrop) the effects of the substance on the neuronal respiratory chain were investigated. The activity of the electron transport system of the respiratory chain was measured by the conversion of the ether to the enolether bond (plasmalogen) of ethanolamine containing glycerophosphatides. Piracetam enhances the formation of ethanolamine-plasmalogen from the corresponding ether lipid by neuronal microsomes and thus resembles the action of cytochrome b5. The addition of antibody against cytochrome b5 was able to inhibit the piracetam-dependent stimulation of the plasmalogen biosynthesis. Thus it appears that the stimulatory effect of piracetam on the formation of ethanolamine-plasmalogen is mediated by an increased synthesis or turnover of cytochrome b5.
Nootropyl (Piracetam) a drug reported to facilitate learning in animals was tested for its effect on man by administering it to normal volunteers. The subjects were given 3x4 capsules at 400 mg per day, in a double blind study. Each subject learned series of words presented as stimuli upon a memory drum. No effects were observed after 7 days but after 14 days verbal learning had significantly increased.
The effects of Piracetam, Naftidrofuryl and methamphetamine on several parameters of cerebral energy metabolism have been studied. At variance with some reports in the literature neither Piracetam nor Naftidrofuryl affected the cerebral contents of adenine nucleotides and, accordingly, both substances were without effect on the adenylate energy charge. This disagreement is explained by methodological differences. Methamphetamine also had no effect on cerebral adenine nucleotides. Piracetam increased the activity of adenylate kinase (EC.2.7.4.3) in isotonically diluted rat brain homogenates without altering the kM of the enzyme for ADP as substrate. It is concluded that although Piracetam has no effect on the cerebral energy metabolism under normal conditions, it may have a beneficial effect under marginal conditions like those met during hypoxia, by virtue of its adenylate kinase stimulating action. It is suggested that this action is responsible for the protective effect of Piracetam against cerebral hypoxia. It may also be related to the enhancement of acquisition under training conditions where cerebral energy metabolism is disturbed.
The effect of Piracetam (UCB 6215, 2-pyrrolidoneacetamide) on learning mediated by transcommissural information flow was studied in hooded rats. Acquisition of monocular pattern discrimination was faster in drug-treated rats (100 mg/kg, 30 min before training) than in untreated controls. Subsequent relearning with one hemisphere functionally eliminated by cortical spreading depression showed that the strength of the primary engram formed under Piracetam in the hemisphere contralateral to the trained eye remained unaffected but that the secondary trace (in the ipsilateral hemisphere) was considerably improved and almost equalled the primary one (savings increased from 20-30% to 50-60%). Learning with uncrossed optic fibers was unaffected by the drug. Interhemispheric transfer of lateralized visual engrams acquired during functional hemidecortication was facilitated by Piracetam administration preceding the five transfer trials performed with the untrained eye open (imperative transfer). Piracetam was ineffective when the trained eye was open during transfer trials (facultative transfer). After a visual engram had been lateralized by 5 days of monocular overtraining, Piracetam facilitated formation of the secondary engram induced by 3 interocular transfer trials. It is concluded that Piracetam enhances transcommissural encoding mechanisms activated in the initial stage of monocular learning and in some forms of interhemispheric transfer, but does not affect the transcommissural readout. This effect is interpreted as a special case of the Piracetam-induced facilitation of the phylogenetically old mechanisms of redundant information storage which improve liminal or subnormal learning.
— 2-Hydroxy-, 2-chloro-, 2- and Cmethyl-GABA are linear competitive inhibitors of GABA uptake in rat brain slices. These analogues are thus potential substrates for the GABA transport system and possible‘false transmitters'. 2-Hydroxy-GABA is the most potent inhibitor of GABA uptake yet described. No specific inhibitor of GABA uptake was revealed amongst the drugs tested.
The integrative activity of the brain is particularly related to the telencephalic level of CNS. Drugs affecting learning and memory usually interfere with the reticular or limbic system, and are either stimulants or sedatives. In contrast, Piracetam (U C B 6215) is an atoxic compound which, up to dosages such as g/kg, does not interfere with autonomic functions, general behavior, level of wakefulness, the limbic system, etc. Yet, in dosages such as mg/kg it improves several learning and memory abilities, protects against experimental amnesic agents, facilitates EEG recovery after severe hypoxia and also facilitates interhemispheric transfer (transcallosal evoked potential and learned behavior). Discussion is made on the basis of the particular neuropharmacology as well as on the available biochemical and human clinical correlations to emphasize the selectivity of this compound on telencephalic integrative mechanisms. Piracetam is presented as the first-comer of a new psychotropic class for which the termnootropic is proposed.
Pattern discrimination learning in functionally hemidecorticate rats leads to formation of memory traces in the intact hemisphere. The interhemispheric transfer (IHT) of such lateralized engrams is more efficient when the untrained eye rather than the trained eye is used during interdepression training (10 trials) preceding the retention test with the contralateral hemisphere, probably because the untrained hemisphere is indispensable for readout in the first case (imperative IHT) but can be completely bypassed in the second case (facultative IHT). Monocular acquisition of a pattern discrimination habit induces a strong primary engram in the contralateral and a weak secondary engram in the ipsilateral hemicortex. The primary trace is further improved with overtraining while the secondary engram is abolished. During interocular transfer, the primary trace is at first read out through commissural fibers while a secondary trace is rapidly transferred to the untrained hemisphere. Pretraining administration of 2-pyrrolidone acetamide (Piracetam, 100 mg/kg) improves the secondary trace acquired during monocular pattern discrimination learning almost to the level of the primary trace, and facilitates the imperative IHT. Uncrossed optic projections and subcortical storage may contribute to IHT of brightness but not of pattern discrimination. It is concluded that IHT of visual engrams is mainly due to transcommissural encoding activated during learning or by transcommissural readout of lateralized traces.
A considerable amount of evidence indicates that the brain tryptophan level depends on circulating tryptophan. Changes of tryptophan concentration have also been described to modify the activity of benzodiazepines and tricyclic antidepressants. In the present study, a series of psychoactive drugs have been preliminarily screened for their activity on brain and plasma tryptophan levels. The results obtained suggest that tryptophan may be involved to varying extents in the activity of different psychoactive compounds.
Piracetam has bee administered to young and old mice to investigate whether the age may differently modulate the activity of this centrally acting drug. After piracetam administration, old mice showed a notably greater increase of their brain tryptophan than young animals. Furthermore, piracetam significantly improves the learning capacity of young mice, but the drug is remarkably more active in improving the performance by old mice. These facts may then suggest that this compound is especially effective in restoring the neurobiological setting of the aging brain.
In a double-blind trial according to a switchback design with 4 periods of one week each a comparison was made between the effects of piracetam and a placebo. In 22 patients with vertigo of central origin (posttraumatic, psychogenic, ecileptogenic and hypertensive vertigo were excluded) piracetam was found to significantly reduce symptoms. On anamnestic examination the patients noted the effect of both substances on vertigo, motility disturbances, vitality and sleep. Piracetam was found to have a significant effect on the first three. The effect of piracetam is explained by an enhanced control of the cerebral cortex on the subordinated vestibular centers, in agreement with findings in the literature on animal and human pharmacology.
Animal models of age-related cognitive impairments
- Bartus
Effects of a nootropic drug in patients affected by hemiplegia after stroke during rehabilitation treatment
- Dolce
Increased verbal learning in dyslexic and control subjects using piracetam (ucb 6215)
- Wilsher