Barbiturate reversal of amino acid antagonism produced by convulsant agents

Abstract

THE hypnotic and anticonvulsant properties of pentobarbitone and related barbiturates may be closely associated with the actions of γ-aminobutyric acid (GABA)^1–3, an inhibitory transmitter at both pre- and postsynaptic receptors in the mammalian central nervous system⁴. Pentobarbitone prolongs pre-⁵ and postsynaptic³ inhibition as well as hyperpolarising central neurones^2,3. Although it has been suggested that pentobarbitone prolongs synaptic inhibition by delaying the removal of GABA from the synaptic cleft^3,6 a direct action of pentobarbitone on GABA receptors cannot be excluded². We have explored this possibility both in the rat isolated sympathetic superior cervical ganglia preparation, which possesses GABA receptors analogous to those in the mammalian brain⁷, and in vivo on single neurones in the rat brainstem. In these experiments pentobarbitone, in amounts which produced no apparent GABA-mimetic effects, reversed the actions of bicuculline methochloride (BMC), a selective GABA antagonist.