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

J Neurochem. 1992 Apr;58(4):1199-204. doi: 10.1111/j.1471-4159.1992.tb11329.x.


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.

MeSH terms

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


  • Glutamates
  • Psychotropic Drugs
  • Receptors, Glutamate
  • Receptors, Neurotransmitter
  • Ibotenic Acid
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Calcium