Because of reports that both barbiturates and ethanol interact with the GABA-benzodiazepine-Chloride channel complex, we embarked on a series of studies to determine if agents which block various aspects of the complex might reduce toxicity from high doses of these sedatives. We previously reported on two chloride channel blockers (IPPO and TBPS) which can reduce mortality due to pentobarbital in mice and have relatively low toxicities when given alone. We have begun to study respiration in rats as a possible cause of the lethal effects of sedatives. We found dose-dependent decreases in respiration rate with both pentobarbital and flurazepam. We are currently studying the effects of chloride channel blockers on this depression of respiration.
