γ-Vinyl GABA: comparison of neurochemical and anticonvulsant effects in mice

摘要: Biochemical and pharmacological effects ofγ-vinyl GABA (Vigabatrin®, GVG), an irreversible enzyme-activated inhibitor of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T), were measured in mice. This anticonvulsant produced a time- dose-dependent elevation the GABA, phenylalanine lysine contents cortical tissue simultaneously decreased glutamate, aspartate alanine levels. In addition, GVG caused biphasic change glutamine concentrations (a decline 1–4 hours after administration, followed 20 later by increase). Moreover, we found new, as yet unidentified amino acid brain eluting with same retention time α-aminoadipic from HPLC cation-exchange column. The level this novel chemical entity was greatly increased injection drug. At all tested intervals between 1 60 injection, ineffective against maximal electroshock. GABA-T dose-dependently protected mice isoniazid-induced seizures, causing increase concentrations. However, apparent correlation applied only until 4 treatment. To better define profile GVG, groups treated, 1, 2, 4, 24 prior to challenge convulsant doses strychnine, pentetrazole (PTZ), picrotoxin, levels, including measured. instances, dependency increases levels differed. Amino animals treated similar those given convulsant. showed no selectivity for seizures impairment GABA-ergic neurotransmission. Although is effective inhibitor, it apparently affects several other pyridoxal-phosphate-dependent cerebral enzymes and/or interacts neurotransmitter systems well.