Potentiation of gamma-vinyl GABA (vigabatrin) effects by glycine

Vigabatrin, because of its ability to increase brain GABA concentration, acts as an anticonvulsant on convulsive epileptic seizures and increases seizures in generalized non-convulsive epilepsy. Next to GABA, glycine is one of the most important inhibitory neurotransmitter amino acids. We studied the influence of glycine on the effects of treatment with vigabatrin in two rat models of generalized convulsive seizures and a rat model of spontaneous generalized non-convulsive seizures. Glycine (750 mg/kg i.p.) or vigabatrin (200 mg/kg i.p.), when given alone, provided partial protection against convulsive seizures, while combined treatment with the two drugs significantly suppressed the convulsive seizures in both the mercaptopropionic acid (MPA)-induced seizures and audiogenic seizures. In contrast to the response to treatment with each individual drug, the drug combination nearly abolished the appearance of isolated spikes on the EEG in MPA seizures. On the other hand, glycine also enhanced the aggravating effect of vigabatrin on spontaneous spike and wave discharges in a rat model of genetic absence epilepsy, whereas glycine or vigabatrin alone, at the above doses, produced only a slight, non-significant increase in spontaneous spike and wave discharges. The GABA-glycine interaction is the first example of a synergistic action of two inhibitory neurotransmitters on seizure-related pathological discharges.