Pharmacodynamics of benzodiazepines

Abstract

Twenty benzodiazepines (BDZs) are at present registered in the RSA. They are anxiolytic, sedative, hypnotic, anticonvulsant and possibly muscle relaxant. Structure-activity relationships are important in modelling BDZ molecules for optimum binding to receptors. Electrophysiological, behavioural and neurochemical effects of BDZs are good indicators of therapeutic potential, and help to elucidate mechanism(s) of action. Specific BDZ receptors on neurons (gamma-aminobutyric acid (GABA)-receptor-associated) and on astrocytes (not associated with GABA receptors) exist in the mammalian central nervous system. BDZs enhance GABA neurotransmission. Selective BDZ antagonists (e.g. Ro 15-1788) are important as research tools, and potentially as diagnostic aids and therapeutic agents. Other possible mechanisms for BDZ action include the roles of adenosine and serotonin. Endogenous BDZ-receptor ligands (e.g. inosine, hypoxanthine, nicotinamide) may be important, but the physiological role of BDZ receptors remains speculative.