Several classes of centrally acting convulsant, depressant, anticonvulsant and anxiolytic drugs modulate GABAergic transmission. The post-synaptic receptor with which these drugs interact in an allosteric complex with distinct binding sites for GABA, benzodiazepines, picrotoxinin and related compounds. Convulsants which inhibit GABA transmission (except bicuculline) inhibit competitively the binding of dihydropicrotoxinin (DHP) or t-butylbicyclophosphorothionate (TBPT) to the picrotoxinin site and prevent the allosteric enhancing effect of depressant drugs on GABA and benzodiazepine binding. Depressant drugs give a mixed inhibition of TBPT binding. The possible topography of the picrotoxinin site and its relationship to convulsant/depressant drug action at the benzodiazepine-GABA receptor-ionophore complex is discussed.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)