γ‐VINYL GABA (4‐amino‐hex‐5‐enoic acid), A NEW SELECTIVE IRREVERSIBLE INHIBITOR OF GABA‐T: EFFECTS ON BRAIN GABA METABOLISM IN MICE¹

Abstract

Abstract— γ‐Vinyl GABA (4‐amino‐hex‐5‐enoic acid, RMI 71754) is a catalytic inhibitor of GABA‐T in vitro. When given by a peripheral route to mice, it crosses the blood‐brain barrier and induces a long‐lasting, dose‐dependent, irreversible inhibition of brain GABA transaminase (GABA‐T). Glutamate decarboxylase (GAD) is only slightly affected even at the highest doses used. γ ‐Vinyl GABA has little or no effect on brain succinate semialdehyde dehydrogenase, aspartate transaminase and alanine transaminase activities. GABA‐T inhibition is accompanied by a sustained dose‐dependent increase of brain GABA concentration. From the rate of accumulation of GABA it was estimated that GABA turnover in brain was at least 6.5 μmol/g/h. Based on recovery of enzyme activity the half‐life of GABA‐T was found to be 3.4 days, that of GAD was estimated to be about 2.4 days. γ ‐Vinyl GABA should be valuable for manipulations of brain GABA metabolism.