Co-administration of gamma-vinyl GABA and cocaine: Preclinical assessment of safety

Gamma-vinyl GABA (GVG, Vigabatrin), an irreversible inhibitor of GABA trans aminase (GABA-T) that inhibits cocaine-induced place preference and self ad ministration has been proposed as a treatment for cocaine addiction. It was therefore important to assess if there was an enhanced toxicity from the c ombination of GVG with cocaine. No mortality was observed with administrati on of GVG (60 mg/kg IV) alone (n=8) or in combination (n=6) with cocaine (5 mg/kg IV). Cocaine-induced EKG alterations were not affected by GVG pretre atment. Plasma alanine amino transferase activity was reduced by GVG treatm ent and this was not further modified by cocaine administration. These resu lts suggest that acute co-administration of GVG and cocaine does not result in immediate cardiovascular or hepatic toxicity of sufficient significance , to preclude further clinical trials.