Binding of 3H-DMCM to benzodiazepine receptors; chloride dependent allosteric regulation mechanisms

Abstract

DMCM is a convulsant agent with negative efficacy at benzodiazepine (BZ) receptors. 3H-DMCM binds to benzodiazepine receptors in vitro. The sensitivity of 3H-DMCM binding to agents presumed to act on chloride channels associated with the BZ/GABA-receptor-complex was investigated at 37 degrees C. Chloride ions (200 mM) enhanced the specific binding of 3H-DMCM four-fold. Similarly the specific binding of 3H-DMCM was enhanced by picrotoxinine in the absence but not in the presence of chloride ions. (+)-Etomidate and pentobarbital reduced the specific 3H-DMCM binding in a partially chloride ion dependent and picrotoxinine sensitive manner. The results obtained are consonant with the idea that 3H-DMCM binds to the BZ/GABA-receptor-chloride ionophor complex; furthermore, binding of 3H-DMCM seems to involve a chloride dependent allosteric regulation mechanism.