Drugs acting as modulators of neurochemical mechanisms of gabaergic synaptic transmission.

Some centra1 effects o/ a variety of GABA related druqs (phenybut, pantogam, piracetarn, aminooxyacptic acid and sodium valproate) u)as studied on mice and rats. N o correlation was found between the total GABA content in the brain and the tranquillizing rffect displayed hy sodium valproate. Iuc3reased brain GABA level, protluced by AOAA, seem.s to be correla,ted with a genera1 " sedation " of animals, but not with a n "anxiolyt ic" effect. Valproate was shown to be the most efìment antaqonist o/ tl~ioserniearbazide and bicueulline convulsions. I t was o/ interest that vnlproate toas demonstrated to impair the trace fixation of memory in rats (passive avoidanw techniqw). The lipophilic phenylderivative of GABA (phenybut) u a s shmun to produce n i th in mioromolar concentration rmqe a pronmunced increase in the efflux of [ i I f E GABA from superfused rat brain coviex synaptosomcs. Th i s effect i s probably due to the involvem.ent of an nnknmun mechanism., operating at the presynaptic terminals of gabaergic neurons.