Vigabatrin

Vigabatrin is an irreversible GABA transaminase (GABA-T) inhibitor.¹ It inhibits rat brain GABA-T when used at a concentration of 0.1 mM. Vigabatrin is selective for rat brain GABA-T over P. fluorescens GABA-T at 10 mM and is 100-fold selective over rat brain glutamic acid decarboxylase (GAD). Vigabatrin (1,500 mg/kg) decreases brain GABA-T activity without affecting GAD activity in mice.² It reduces the incidence of myoclonus in a mouse model of audiogenic seizures.³ Vigabatrin also increases the electroconvulsive threshold in mouse model of maximal electroshock-induced seizures and reduces the number of clonic convulsions induced by pentylenetetrazol in mice.⁴ Formulations containing vigabatrin have been used in the treatment of seizures and infantile spasms.

1.Lippert, B., Metcalf, B.W., Jung, M.J., et al.4-Amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brainEur. J. Biochem.74(3)441-445(1977) 2.Jung, M.J., Lippert, B., Metcalf, B.W., et al.g-Vinyl GABA (4-amino-hex-5-enoic acid), A new selective irreversible inhibitor of GABA-T: Effects on brain GABA metabolism in miceJ. Neurochem.29(5)797-802(1977) 3.Meldrum, B.S., and Murugaiah, K.Anticonvulsant action in mice with sound-induced seizures of the optical isomers of g-vinyl GABAEur. J. Pharm.89(1-2)149-152(1983) 4.Luszczki, J.J., and Czuczwar, S.J.Isobolographic characterization of interactions between vigabatrin and tiagabine in two experimental models of epilepsyProg. Neuropsychopharmacol. Biol. Psychiatry31(2)529-538(2007)