Cu2+ is the active principle of an endogenous substance from porcine cerebral cortex which antagonizes the anticonvulsant effect of diazepam.
A boiled extract of porcine cerebral cortex was fractionated on Sephadex G-75 and LH-20 followed by paper chromatography of the active fraction having inhibitory activity towards [3H]GABA binding to rat brain synaptic membranes. A ninhydrin-negative substance migrating more quickly than authentic GABA was identified as a copper-GABA complex. The complex inhibited specific [3H]GABA binding (IC50 approximately equal to 1 microM) and antagonized the anticonvulsant effect exerted by intraamygdaloid injection of diazepam. The effect of a synthetic copper-GABA complex was compared and found to be similar to the endogenous complex. Cu2+ alone has no affinity for the GABA recognition site but antagonizes the anticonvulsant effect of diazepam. Therefore, Cu2+ is suggested to be the pharmacologically active principle of the endogenous substance. Cu2+ does not seem to function via the recognition site of the GABA receptor.
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000378:metabolism; D002540:Cerebral Cortex / Q000032:analysis*; D003300:Copper / Q000494:pharmacology*; D003975:Diazepam / Q000037:antagonists & inhibitors*; D018756:GABA Antagonists; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D013570:Synaptic Membranes / Q000378:metabolism
D018756:GABA Antagonists; D011963:Receptors, GABA-A; D003300:Copper; D003975:Diazepam