Effects of 1-amino-5-bromouracil (cas 127984-93-4) on the benzodiazepine-GABAA receptor complex

Add time:08/21/2019    Source:sciencedirect.com

We investigated the effects of 1-amino-5-bromouracil (cas 127984-93-4) on the benzodiazepine-γ-aminobutyric acid (GABA)A receptor complex to elucidate its central action. 1-Amino-5-bromouracil neither displaced nor enhanced [3H]muscimol, [35S] t-butylbi-cyclophosphorothionate (TBPS), or [3H]dehydroepiandrosterone sulfate binding to the rat brain synaptosomal membranes. The anesthesia induced by 1-amino-5-bromouracil was potentiated by diazepam, pentobarbital, and muscimol, and was antagonized by picrotoxin but not by bicuculline. 1-Amino-5-bromouracil protected mice from picrotoxin-induced seizure and slightly ameliorated TBPS-induced seizure, but did not antagonize bicuculline-induced seizure. Diazepam antagonized both the bicuculline- and the picrotoxin-induced seizure, and pentobarbital antagonized the picrotoxin- and the TBPS-induced seizure. Our in vivo studies suggest that part of the central action of 1-amino-5-bromouracil is concerned with the benzodiazepine-GABAA receptor complex including the chloride channel.

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