The “nootropic” approach to the pharmacology of the integrative activity of the brain 1, 2

Giurgea, C.

doi:10.1007/bf03000311

Cited by 108 publications

(19 citation statements)

References 5 publications

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“…Piracetam was the first nootropic agent discovered 26 and was found originally to be effective as a protective agent in hypoxia-induced amnesia. 27 Although it affects a number of neuronal proteins, some evidence suggests that it can act at AMPA receptors. 28,29 Aniracetam, another member of the racetam family of drugs, is considerably more potent and acts directly on AMPA receptors.…”

Section: Introductionmentioning

confidence: 99%

“…Piracetam was the first nootropic agent discovered and was found originally to be effective as a protective agent in hypoxia-induced amnesia . Although it affects a number of neuronal proteins, some evidence suggests that it can act at AMPA receptors. , Aniracetam, another member of the racetam family of drugs, is considerably more potent and acts directly on AMPA receptors. , Aniracetam and other allosteric modulators of AMPA receptors can block or slow desensitization, slow deactivation, and enhance synaptic plasticity. , These characteristics have led to clinical trials of several drugs for Alzheimer’s disease and attention deficit disorder, , but only aniracetam is available for mild dementia in Europe .…”

Section: Introductionmentioning

confidence: 99%

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Piracetam Defines a New Binding Site for Allosteric Modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic Acid (AMPA) Receptors

Ahmed

Oswald

2010

J. Med. Chem.

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Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system and are important potential drug targets for cognitive enhancement and the treatment of schizophrenia. Allosteric modulators of AMPA receptors promote dimerization by binding to a dimer interface and reducing desensitization and deactivation. The pyrrolidine allosteric modulators, piracetam and aniracetam, were among the first of this class of drugs to be discovered. We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to both GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity. However, the binding sites for piracetam and aniracetam differ considerably. Aniracetam binds to a symmetrical site at the center of the dimer interface. Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators. This new site may be of importance in the design of new allosteric regulators.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Piracetam Defines a New Binding Site for Allosteric Modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic Acid (AMPA) Receptors

Ahmed

Oswald

2010

J. Med. Chem.

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“…The first prototypical nootropic agent, piracetam (Figure 1), is currently the most commonly used drug to treat cognitive impairments (Giurgea, 1973; Tripathi et al, 2017). The drug represents a cyclic derivative of the gamma-aminobutyric acid (GABA) (Winblad, 2005), a major inhibitory neurotransmitter.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological characterization of a novel putative nootropic beta-alanine derivative, MB-005, in adult zebrafish

et al. 2022

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Background: Cognitive deficits represent an urgent biomedical problem, and are commonly reduced by nootropic drugs. Animal models, including both rodents and zebrafish, offer a valuable tool for studying cognitive phenotypes and screening novel nootropics. Beta-alanine and its derivatives have recently been proposed to exert nootropic activity. Aims: This study aimed to characterize putative nootropic profile of a novel β-alanine analogue, 1,3-diaminopropane (MB-005), in adult zebrafish. Methods: Nootropic profile of MB-005 was assessed in adult zebrafish in the novel tank and conditioned place aversion (CPA) tests acutely, and in cued-learning plus-maze (PMT) tests chronically. Results/Outcomes: MB-005 did not alter zebrafish anxiety-like behavior or monoamine neurochemistry acutely, improved short-term memory in the CPA test, but impaired cognitive performance in both CPA and PMT tests chronically. Conclusions/Interpretation: This study reveals high sensitivity of zebrafish cognitive phenotypes to MB-005, suggesting it as a potential novel cognitive enhancer acutely, but raises concerns over its cognitive (and, possibly, other) side-effects chronically.

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“…Racetam molecules represent a family of pharmacologically active 2-pyrrolidinones. − These compounds, enhancing cognition properties and possessing a large prescription field, are particularly attractive synthetic targets for the pharmaceutical industry …”

Section: Introductionmentioning

confidence: 99%

Continuous Flow Electrochemical Oxidative Cyclization and Successive Functionalization of 2-Pyrrolidinones

Quertenmont

Toussaint

Defrance

et al. 2021

Org. Process Res. Dev.

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2-Pyrrolidinones are important scaffolds found in numerous pharmacologically active compounds, such as brivaracetam and levetiracetam (antiepileptic drugs) or piracetam and pramiracetam (age-related memory impairment drugs). Among the numerous targets, nootropic agents represent an attractive class of compounds since they selectively improve cognitive functions. In this study, we report the successful translation of an electrochemical batch oxidative cyclization/functionalization of 2pyrrolidinones, using the Kolbe reaction, from a batch type cell to a continuous flow electrochemical reactor. Combining organic electrosynthesis with continuous flow chemistry offers numerous advantages over batch electrolysis such as a faster reaction time and better mixing of the heterogeneous reaction. Moreover, due to the use of continuous flow electrochemical cells, which have a precise geometry, a small interelectrode gap, and large electrode surface area to reactor volume ratio, the productivity of organic electrosynthesis can be easily improved. Additionally, the translation of a batch electrochemical transformation to a continuous flow reactor is a critical step in the development of an electrochemical process given that flow chemistry is the most straightforward approach for the scale-up of this type of reactions. In this study, the application of continuous flow electrochemistry in our process allowed for an excellent productivity of 0.40 g/(h•mL) and an up to 81% yield of 2-pyrrolidinone within a loop-reactor setup (equipped with a 5 mL container).

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The “nootropic” approach to the pharmacology of the integrative activity of the brain 1, 2

Cited by 108 publications

References 5 publications

Piracetam Defines a New Binding Site for Allosteric Modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic Acid (AMPA) Receptors

Piracetam Defines a New Binding Site for Allosteric Modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic Acid (AMPA) Receptors

Pharmacological characterization of a novel putative nootropic beta-alanine derivative, MB-005, in adult zebrafish

Continuous Flow Electrochemical Oxidative Cyclization and Successive Functionalization of 2-Pyrrolidinones

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