Synergy or potentiation of sodium valproate and an inhibitor of GABA uptake

Abstract

(R,S)-nipecotic acid, which inhibits GABA uptake in vitro, has only a slight effect on mouse-killing behaviour. (R,S)-nipecotamide maleate (NCS-3), injected IP (50–150 mg/kg) or per os (0.5-1.5 g/kg) to muricidal rats produces an inhibition of this agressive behaviour. Coadministration of suboptimal doses of NCS-3 and the GABA-inhibitor sodium valproate produce a marked potentiation when given by the intraperitoneal route and a striking synergistic effect when given orally. This results provide supplementary evidence that the inhibition of killing behaviour by these drugs is due to a potentiation of a central GABA-ergic system.