Interaction of piracetam with several neurotransmitter receptors in the central nervous system. Relative specificity for 3H-glutamate sites

Abstract

The influence of the nootropic drug piracetam (Normabrain) on specific ligand binding to several neurotransmitter and drug receptors was investigated using established receptor binding procedures. Even at concentrations of 20 mmol/l of piracetam no or only marginal inhibition was observed for the dopamine- and muscarinic cholinergic receptors and for the peripheral benzodiazepine binding site, while for the benzodiazepine receptor, the GABA receptor, the opiate receptor, and the serotonin receptor half-maximal inhibitory concentrations between 20 and 50 mmol/l could be determined. In contrast to these effects seen only at relatively high piracetam concentrations, piracetam is considerably more active at the L-glutamate receptor with a half-maximal inhibitory concentration of about 1 mmol/l. This relatively specific effect of piracetam at the L-glutamate receptor could also take place under therapeutic conditions in vivo, since brain levels of piracetam in man may range between 0.1 and 1 mmol/l. It is concluded that effects within the glutaminergic system of the brain could contribute to the therapeutical effects of piracetam in man.