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

A. Copani, A. A. Genazzani, G. Aleppo, G. Casabona, P. L. Canonico, U. Scapagnini, F. Nicoletti

Research output: Contribution to journalArticlepeer-review

Abstract

Micromolar concentrations of piracetam, aniracetam, and oxiracetam enhanced α-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.

Original languageEnglish
Pages (from-to)1199-1204
Number of pages6
JournalJournal of Neurochemistry
Volume58
Issue number4
Publication statusPublished - Apr 1992

Keywords

  • α-[H]amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding
  • α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
  • Ca influx
  • Aniracetam
  • Nootropic drugs
  • Oxiracetam
  • Piracetam

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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