A comparative study of some convulsant substances as gamma-aminobutyric acid antagonists in the feline cerebral cortex.

1. By the use of microiontophoretic techniques, quantitative estimates were obtained of the depressant effects of gamma-aminobutyric acid (GABA) on single feline cortical neurones.2. Picrotoxin, bicuculline, strychnine, (+)-tubocurarine, penicillin and leptazol were also applied microiontophoretically to single neurones. Sequential GABA applications were made before, during and after the microiontophoresis of these substances and any effects on the time course of the GABA depression were measured as an estimate of antagonism or potentiation of GABA.3. (+)-Tubocurarine was found to be a potent GABA antagonist. Picrotoxin and bicuculline were rather less potent and strychnine and penicillin only weakly active as GABA antagonists. Leptazol appeared to be inactive against GABA depressions.4. In addition, bicuculline and strychnine were found to be capable of potentiating the depressant action of GABA. This property was not shared by the other substances studied.5. All the substances studied produced changes in neuronal firing rate that did not correlate with GABA antagonism.6. In conclusion, several potent convulsants have been shown to be capable of GABA antagonism. It is not yet clear that this effect, rather than a direct effect on neuronal excitability, is the prime mechanism behind their convulsant properties.