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  • Title: Biological substrates of anxiety: benzodiazepine receptors and endogenous ligands.
    Author: Paul SM, Marangos PJ, Skolnick P, Goodwin FK.
    Journal: Encephale; 1982; 8(2):131-44. PubMed ID: 6125374.
    Abstract:
    Benzodiazepines have been shown to produce most, if not all, of their pharmacological effects by directly interacting with specific recognition or receptor sites within the CNS. The presence of benzodiazepine receptors has prompted many studies as to their possible physiological significance, including attempts at isolating an endogenous ligand. To data a number of substances including the purines inosine and hypoxanthine, nicotinamide, beta-carbolines, and an unidentified peptide factor have been isolated and postulated as being endogenous ligands. A number of these compounds have also been shown to either mimic or antagonize the behavioral effects of benzodiazepines, although it is still unclear whether these occur under physiological conditions. More recent biochemical studies have established a functional (and perhaps structural) relationship between te benzodiazepine receptor and the receptor for gamma amino butyric acid (GABA), the major inhibitory neurotransmitter in brain. It now appears that the benzodiazepine receptor actually exists as a "supramolecular complex" consisting of a GABA receptor and an associated chloride channel. A number of anxiolytic drugs including the barbiturates and pyrazolopyridines appear to act through these associated "regulatory" sites rather than directly on the benzodiazepine recognition site.
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