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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

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 (US)
Pages (from-to)1199-1204
Number of pages6
JournalJournal of Neurochemistry
Volume58
Issue number4
DOIs
StatePublished - Jan 1 1992

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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