Effect on GABAa receptors

A class of sedative/hypnotic type drug that exert their effects through the benzodiazepine binding site on GABAa receptors. The class consists both of molecules that contain the benzodiazepine moiety, for example diazepam, lorazepam and flunitrazepam, and the newer, non-benzodiazepine compounds such as zolpidem, zopiclone, indiplon and zaleplon. BzRAs are primarily used for the treatment of anxiety, insomnia and to elicit varying levels of sedation. The wide selection of compounds currently available affords the prescribing clinician extensive options in terms of relative efficacies and durations of action. 

Buck KJ, Harris RA Benzodiazepine agonist and inverse agonist actions on GabaA receptor-operated chloride channels, 11 chronic effects of ethanol. J Pharmacol Exp Ther 253 713-719, 1990... 

Clonazepam, U5P. Clonazepam S-(2-chlorophenyl)-3-dihydro-7-nitro-2//-1,4-benzodiazpin-2-one (iCIonopin). partially selective at benzodiazepine allosteric binding sites on GABAa receptors, is useful in ab.sence seizures and in myoclonic seizures. Tolerance to the anticonvulsant effect often develops, a common problem with the benzodiazepines. Metabolism involves hydroxylation of the 3 position, followed by glucuronidation and nitro group reduction, followed by acetylation. 

The (-I-) enantiomer of isofiurane appears to be more potent as an anesthetic agent than is its antipode [192,193]. It appears that the (-I-) enantiomer causes a greater inhibition of neuronal activity by stimulation of GABAa receptors in the central nervous system [194]. Compared to isoflurane, halothane enantiomers do not appear to differ as much in their effects on GABAa responses [195]. 

The definition of desired therapeutic and side effects in the case of the benzodiazepines very much depends on the clinical problem in question. The sedative and hypnotic actions are desired effects in the treatment of insomnia, but undesired effects in the treatment of anxiety disorders. Effects that are usually undesired include daytime drowsiness, potentiation of the sedative effects of ethanol, and anterograde amnesia. They are mediated via the benzodiazepine site of GABAa receptors, since they can be antagonized with flumazenil. 

Neurosteroids prolong the mean open time of recombinant GABAa receptor channels. Whereas, at least in recombinant systems, the identity of the a and (3 subunits has little or no effect on neurosteroid action, substitution of the y subunit by a 8 subunit suppresses the GABA-modulatory activity of the neurosteroids. 

Meredith TJ, Ruprah M, Liddle A, et al Diagnosis and treatment of acute poisoning with volatile substances. Hum Toxicol 8 277-286, 1989 Merry J, Zachariadis N Addiction to glue sniffing. Br Med J 5317 1448, 1962 Mihic SJ Acute effects of ethanol on GABAA and glycine receptor function. Neuro-chemint 35 115-123, 1999... 

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