THE EFFECT OF 4‐AMINO HEX‐5‐YNOIC ACID (γ‐ACETYLENIC GABA, γ‐ETHYNYL GABA) A CATALYTIC INHIBITOR OF GABA TRANSAMINASE, ON BRAIN GABA METABOLISM <i>IN VIVO</i>

Abstract— 4‐Amino hex‐5‐ynoic acid (γ‐acetylenic GABA, γ‐ethynyl GABA, RM171.645), a catalytic inhibitor of GABA transaminase in vitro , induces a rapid, long‐lasting dose‐dependent decrease of GABA transaminase activity and, to a lesser extent, of glutamate decarboxylase activity in the brains of rats and mice when given by a peripheral route. The GABA concentration in whole brain increases up to 6‐fold over control values. The action of γ‐acetylenic GABA is relatively specific, as no in vivo inhibition of brain aspartate and alanine transaminase activities could be detected. Furthermore, the amount of radioactive drug bound to the protein fraction of brain homogenate is of the same order of magnitude as that of the GABA transaminase present, as calculated from total GABA transaminase activity, molecular weight and specific activity of the pure enzyme. γ‐Acetylenic GABA illustrates the usefulness of a catalytic irreversible enzyme inhibitor in altering neurotransmitter metabolism in vivo .