Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures.
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.
Copani
A
A
Institute of Pharmacology, University of Catania School of Medicine, Italy.
Genazzani
A A
AA
Aleppo
G
G
Casabona
G
G
Canonico
P L
PL
Scapagnini
U
U
Nicoletti
F
F
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D011619:Psychotropic Drugs; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002118:Calcium