GABAA-benzodiazepine receptors: demonstration of pharmacological subtypes in the brain.

Abstract

The GABAA receptor is a ligand-gated chloride ion channel that mediates the majority of rapid-acting inhibitory synapses in the central nervous system (Olsen and Venter, 1986). The GABAA receptors are also the target of numerous clinically important depressant and excitatory drugs (Olsen, 1981; Tallman and Gallager, 1985; Biggio and Costa, 1988). The convulsant drug bicuculline acts as a competitive antagonist at the GABA recognition site, beta-carbolines block GABA function as ’ inverse agonists’ at the benzodiazepine recognition site, and picrotoxin and cage convulsants inhibit the chloride channel function at a site on the receptor complex distinct from the GABA and benzodiazepine receptor sites. Clinically important depressant benzodiazepines enhance GABA-mediated inhibition via their own binding sites on the receptor complex. Still additional sites on the receptor-ion channel complex mediate the action of barbiturates, steroid anesthetics, and possibly ethanol to enhance GABAA receptor function at the membrane level (Olsen and Venter, 1986; Biggio and Costa, 1988).