Co-administration of gamma-vinyl GABA and cocaine: preclinical assessment of safety.
Gamma-vinyl GABA (GVG, Vigabatrin), an irreversible inhibitor of GABA transaminase (GABA-T) that inhibits cocaine-induced place preference and self administration has been proposed as a treatment for cocaine addiction. It was therefore important to assess if there was an enhanced toxicity from the combination of GVG with cocaine. No mortality was observed with administration of GVG (60 mg/kg i.v.) alone (n=8) or in combination (n=6) with cocaine (5 mg/kg i.v.). Cocaine-induced EKG alterations were not affected by GVG pretreatment. Plasma alanine amino transferase activity was reduced by GVG treatment and this was not further modified by cocaine administration. These results 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.
Molina
P E
PE
Department of Surgery, North Shore University Hospital, Manhasset, NY 11030, USA. molina@bnl.gov
Ahmed
N
N
Ajmal
M
M
Dewey
S
S
Volkow
N
N
Fowler
J
J
Abumrad
N
N
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006439:Hemodynamics / Q000187:drug effects*; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity
D004791:Enzyme Inhibitors; D019344:Lactic Acid; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D000410:Alanine Transaminase; D020888:Vigabatrin; D003042:Cocaine