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 reported last year tht IPPO, a chloride channel blocker, greatly reduced deaths from pentobarbital (PB) overdose and reduced loss of righting reflex from ethanol. We have continued these studies looking for agents which are both more effective, and less toxic when given by themselves. We found that TBPS, also a chloride channel blocker, was equally effective as IPPO but had less toxicity. We are currently investigating adenosine antagonists, in this same paradigm.
