Abstract
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 pharmacodynamic 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.
Keywords: vigabatrin, GABA-T, platelet inhibition
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- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Jeremiah S., Povey S. The biochemical genetics of human gamma-aminobutyric acid transaminase. Ann Hum Genet. 1981 Jul;45(Pt 3):231–236. doi: 10.1111/j.1469-1809.1981.tb00334.x. [DOI] [PubMed] [Google Scholar]
- Jung M. J., Lippert B., Metcalf B. W., Böhlen P., Schechter P. J. gamma-Vinyl GABA (4-amino-hex-5-enoic acid), a new selective irreversible inhibitor of GABA-T: effects on brain GABA metabolism in mice. J Neurochem. 1977 Nov;29(5):797–802. doi: 10.1111/j.1471-4159.1977.tb10721.x. [DOI] [PubMed] [Google Scholar]
- Lippert B., Metcalf B. W., Resvick R. J. Enzyme-activated irreversible inhibition of rat and mouse brain 4-aminobutyric acid-alpha-ketoglutarate transaminase by 5-fluoro-4-oxo-pentanoic acid. Biochem Biophys Res Commun. 1982 Sep 16;108(1):146–152. doi: 10.1016/0006-291x(82)91843-5. [DOI] [PubMed] [Google Scholar]
- Pedersen S. A., Klosterskov P., Gram L., Dam M. Long-term study of gamma-vinyl GABA in the treatment of epilepsy. Acta Neurol Scand. 1985 Sep;72(3):295–298. doi: 10.1111/j.1600-0404.1985.tb00873.x. [DOI] [PubMed] [Google Scholar]
- Rimmer E. M., Richens A. Double-blind study of gamma-vinyl GABA in patients with refractory epilepsy. Lancet. 1984 Jan 28;1(8370):189–190. doi: 10.1016/s0140-6736(84)92112-3. [DOI] [PubMed] [Google Scholar]
- White H. L. 4-aminobutyrate:2-oxoglutarate aminotransferase in blood platelets. Science. 1979 Aug 17;205(4407):696–698. doi: 10.1126/science.462176. [DOI] [PubMed] [Google Scholar]
- White H. L., Sato T. L. GABA-transaminases of human brain and peripheral tissues--kinetic and molecular properties. J Neurochem. 1978 Jul;31(1):41–47. doi: 10.1111/j.1471-4159.1978.tb12430.x. [DOI] [PubMed] [Google Scholar]