Interaction of barbiturates with dihydropicrotoxinin binding sites related to the GABA receptor-ionophore system

摘要: Abstract Barbiturate drugs of diverse chemical structure inhibited the binding [ 3 H] α-dihydropicrotoxinin to rat brain membranes. This biologically active analoque picrotoxin labels membrane sites related convulsant action these in inhibiting GABA postsynaptic receptor-ionophore function at a site distinct from receptor. Depressant barbiturates such as pentobarbital dihydropicrotoxinin competitively therapeutic concentrations (IC 50 = μ M) whereas drug does not alter receptors, uptake, or release this concentration. Antiepileptics phenobarbital =400 M), were weaker inhibitors binding. Convulsant barbiturates, however, dimethylbutylbarbiturate =0.05 and cyclohexylidene-ethyl barbiturate =0.7 potent inhibitors. The displacement radioactive by had different slopes Hill numnbers (0.4) compared depressant picrotoxinin itself (Hill numbers 1.0), indicating heterogeneity negative cooperativity. These intractions with are consistent neurophysiological evidence that may involve modulation CNS inhibitory synaptic transmission level receptor-ionophores.