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Differences in the mechanism of antihypoxic action of benzodiazepine receptor agonists and muscimol


, : Differences in the mechanism of antihypoxic action of benzodiazepine receptor agonists and muscimol. Byulleten' Eksperimental'noi Biologii i Meditsiny 98(10): 436-439

Neuropharmacological analysis of previously revealed antihypoxic activity of benzodiazepines (BDZ) was performed in experiments on mice exposed to hypoxia. Antihypoxic effect of diazepam is shown to be antagonized by the central BDZ receptor blocker, Ro 15-1788 [ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-(1,5-a)-(1,4)-benzodiazepine-3-carboxylate]. A certain degree of antihypoxic activity also abolished by Ro 15-1788 is exhibited by hypothetical ligands of BDZ receptors: inosin, nicotinamide, ethyl-.beta.-carboline-3-carboxylate. The effect of dipiridamole, a drug with high affinity for BDZ receptors of the peripheral type is not antagonized by Ro 15-1788, another evidence of Ro 15-1788 affinity precisely to the central BDZ receptors. GABA-mimetics (muscimol and GABA cetyl ester) were also found to have marked antihypoxic activity. Unlike BDZ receptor agonists, this effect is reduced by bicuculline and not by Ro 15-1788. Antihypoxic activity of BDZ apparently is caused by their direct interaction with the central BDZ receptors, probably with the type which is not modulated by GABAA receptors.

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Accession: 005151383

DOI: 10.1007/bf00808191

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