The effect of vigabatrin on brain and platelet GABA-transaminase activities.
1. The inhibition profiles of GABA-transaminase (GABA-T) in rat brain and platelet have been compared following a single intraperitoneal dose of vigabatrin. The inhibition profiles exhibit similarities. The inhibition produced by the drug is dose-dependent and, in the dose range used in man, the dose-response curves are comparable. The pharmaco-dynamic effects of the drug (inhibition of central and peripheral GABA-T) remain after the drug has been eliminated from plasma. It is suggested that the measurement of rat platelet GABA-T may be used as a non-invasive assessment of the efficacy of GABA-T inhibitors in the rat CNS. 2. Human blood platelet GABA-T was significantly inhibited by the administration of a single oral dose of vigabatrin. Chronic administration also produces a significant inhibition of platelet GABA-T. As with rats, the pharmacodynamic effects on the platelet enzyme remained after the drug had been eliminated from plasma. If the situation in man is assumed to parallel that found in the rat then measurement of platelet GABA-T inhibition could prove to be a useful indicator of central inhibition.
Bolton
J B
JB
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff.
Rimmer
E
E
Williams
J
J
Richens
A
A
D000612:4-Aminobutyrate Transaminase / Q000097:blood / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000614:Aminocaproates / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013997:Time Factors; D020888:Vigabatrin
D000614:Aminocaproates; D000927:Anticonvulsants; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin