Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures.

Article date: 1992/4/1

PubMed ID: 1372342

Journal name: Journal of neurochemistry (ISSN: 0022-3042)


Micromolar concentrations of piracetam, aniracetam, and oxiracetam enhanced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-stimulated 45Ca2+ influx in primary cultures of cerebellar granule cells. Nootropic drugs increased the efficacy but not the potency of AMPA and their action persisted in the presence of the voltage-sensitive calcium channel blocker nifedipine. Potentiation by oxiracetam was specific for AMPA receptor-mediated signal transduction, as the drug changed neither the stimulation of 45Ca2+ influx by kainate or N-methyl-D-aspartate nor the activation of inositol phospholipid hydrolysis elicited by quisqualate or (+-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid. Piracetam, aniracetam, and oxiracetam increased the maximal density of the specific binding sites for [3H]AMPA in synaptic membranes from rat cerebral cortex. Taken collectively, these results support the view that nootropic drugs act as positive modulators of AMPA-sensitive glutamate receptors in neurons.

Author List: Copani A, Genazzani A A, Aleppo G, Casabona G, Canonico P L, Scapagnini U, Nicoletti F

Publication Types: Journal Article

Substances mentioned in the article: Glutamates; Psychotropic Drugs; Receptors, Glutamate; Receptors, Neurotransmitter; Ibotenic Acid; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Calcium;

Mesh terms: Animals; Calcium/metabolism; Cells, Cultured; Cerebral Cortex/cytology; Glutamates/metabolism; Ibotenic Acid/analogs & derivatives; Kinetics; Models, Neurological; Neurons/metabolism; Psychotropic Drugs/pharmacology; Receptors, Glutamate; Receptors, Neurotransmitter/drug effects; Synaptic Membranes/metabolism; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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