Pentylenetetrazol and penicillin are selective antagonists of GABA-mediated post-synaptic inhibition in cultured mammalian neurones

Abstract

PENTYLENETETRAZOL (PTZ) and penicillin (PCN) are potent convulsants commonly used to produce focal or generalised epileptiform discharges in the mammalian central nervous system¹. Investigations of the cellular basis for their con-vulsant effects have been performed in various vertebrate and invertebrate preparations wtih two basic hypotheses dominating the literature: (1) that the convulsant effect is produced by pharmacological actions on synaptic transmissions to reduce inhibition^2–8 and/or to enhance excitation⁹, or (2) that the convulsants directly enhance the excitability of neuronal membranes apart from effects on synaptic transmission^10–16. We have studied the mechanism of their convulsant action in a mammalian tissue culture system and report here that both PTZ and PCN selectively antagonise post-synaptic responses to γ-aminobutyric acid (GABA), a putative inhibitory neurotransmitter¹⁷. The results presented here provide direct evidence derived from the mammalian nervous system that the convulsant action of PTZ and PCN may be due ito a specific pharmacological action on GABA-mediated inhibitory synaptic transmission.