Effects of 1-amino-5-bromouracil on the benzodiazepine-GABAA receptor complex.

Abstract

We investigated the effects of 1-amino-5-bromouracil on the benzodiazepine-gamma-aminobutyric acid (GABA)A receptor complex to elucidate its central action. 1-Amino-5-bromouracil neither displaced nor enhanced [3H]muscimol, [35S]t-butylbicyclophosphorothionate (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.

• Authors: S Miyazaki, M Imaizumi, H Machida
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 271 Issue 1 Pg. 179-84 (Dec 12 1994) ISSN: 0014-2999 [Print] Netherlands
• PMID: 7698200 (Publication Type: Journal Article)

Chemical References

• Anti-Anxiety Agents
• Anticonvulsants
• Bridged Bicyclo Compounds
• Bridged Bicyclo Compounds, Heterocyclic
• Convulsants
• Receptors, GABA-A
• Picrotoxin
• Muscimol
• Dehydroepiandrosterone
• Bromouracil
• tert-butylbicyclophosphorothionate
• 1-amino-5-bromouracil

Topics

• Anesthesia
• Animals
• Anti-Anxiety Agents (antagonists & inhibitors, pharmacology)
• Anticonvulsants (pharmacology)
• Bridged Bicyclo Compounds (antagonists & inhibitors, metabolism, pharmacology)
• Bridged Bicyclo Compounds, Heterocyclic
• Bromouracil (analogs & derivatives, antagonists & inhibitors, pharmacology)
• Convulsants (antagonists & inhibitors, metabolism, pharmacology)
• Dehydroepiandrosterone (metabolism)
• Male
• Mice
• Mice, Inbred ICR
• Muscimol (metabolism, pharmacology)
• Picrotoxin (antagonists & inhibitors, toxicity)
• Radioligand Assay
• Rats
• Rats, Wistar
• Receptors, GABA-A (drug effects)
• Seizures (chemically induced, physiopathology)
• Synaptic Membranes (drug effects, metabolism)