The effect of the convulsant allylglycine (2-amino-4-pentenoic acid) on the activity of glutamic acid decarboxylase and the concentration of GABA in different regions of guinea pig brain

Abstract

Intraperitoneal administration of allylglycine to guinea pigs resulted in convulsions approximately 3 hr later. The concentration of GABA and the activity of GAD were significantly reduced in three brain areas, namely the cochlear nucleus, inferior colliculus and cerebral cortex, with the smallest changes being observed in the cortex. There were large in vitro regional variations in the extent of the allylglycine inhibition in brain areas from guinea pig, cat and rat, with those areas rich in GAD activity being least affected. Endogenous GAD activities in the brain regions were found to be inversely correlated with the percentage allylglycine inhibition (P < 0.005). Other inhibitors of GAD activity i.e. NaCl, Zn 2+ and thiosemicarbazide showed no such regional variation of inhibition. The results suggest that the regional differences in allylglycine inhibition reflect anomalies of the metabolism of the drug per se, and probably do not indicate regional differences in GABA turnover and metabolism.