Abstract
The benzodiazepines have been well characterised as minor tranquillizers and attempts to explain their unique spectrum of activity have included suggestions that they may interact with a variety of neurotransmitter systems1. Recently, a possible interaction with the γ-aminobutyric acid (GABA) system has received most attention. Benzodiazepines potentiate the actions of both synaptically released and exogenously administered GABA2–4 on mammalian neuronal preparations but the site of action within the GABA response mechanism has not been determined. Binding studies suggest that benzodiazepines combine with highly specific sites in the neuronal membrane5 and that these sites have some indirect association with GABA receptors6–11. To investigate this association further in a functioning GABA system, quantitative studies have been made in vitro on neuronal depolarisations mediated by GABA receptor activation. Evidence has already been presented12 that bicuculline is most probably a competitive antagonist at the GABA receptor while picrotoxin acts as an antagonist at a separate site. Here flurazepam is shown to attenuate preferentially the action of picrotoxin rather than bicuculline and a model is suggested for the site of action of these drugs within the GABA response mechanism.
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Simmonds, M. A site for the potentiation of GABA-mediated responses by benzodiazepines. Nature 284, 558–560 (1980). https://doi.org/10.1038/284558a0
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DOI: https://doi.org/10.1038/284558a0
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