Molecular Heterogeneity of GABAA-Benzodiazepine Receptors
Since the introduction of benzodiazepines into clinical use and the establishment of their therapeutic action as anxiolytics, anticonvulsants, muscle relaxants and sedative hypnotics (Randall, 1961) a wealth of information has been accumulated on the molecular mechanism of action of these compounds. Thus, electrophysiological investigations have indicated that benzodiazepines exert most of their actions by enhancing the postsynaptic effects of the putative neurotransmitter GABA (Haefely et al., 1981). Biochemical and pharmacological investigations have established the existence of a high affinity binding site for benzodiazepines in brain membranes (Braestrup and Squires, 1977; Möhler and Okada, 1977) and demonstrated an excellent correlation between the clinical potency of a series of benzodiazepines and their ability to displace 3H-diazepam or 3H-flunitrazepam from their high affinity binding sites. Thus, it was concluded that these sites are the physiological receptors by which benzodiazepines exert their pharmacologically and clinically relevant actions.
KeywordsHigh Affinity Binding Site Sedative Hypnotic Clinical Potency Diazepine Receptor Bovine Cerebral Cortex
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