Some effects of ethanol on the toxicity and distribution of barbiturates in rats

Abstract

The interaction of ethanol with amobarbital, barbital, pentobarbital, phenobarbital, and thiopental was investigated at both the pharmacological and metabolic levels in rats. Induction time was shortened and sleeping time lengthened by the administration of ethanol with each of the five barbiturates, the effects being most pronounced with barbital and phenobarbital. Brain levels of barbital, phenobarbital, acetaldehyde, and acetone were increased by ethanol. Rats given amobarbital, pentobarbital, and thiopental had significantly higher brain and serum barbiturate levels at the time of regain of the righting reflex than was present in rats given these barbiturates with ethanol, indicating that the CNS depression was not dependent only on the concentration of barbiturate in the brain. The decay profiles of serum barbiturate concentrations were not altered by ethanol, and the barbiturates had no effect on the brain and blood ethanol levels. Phenobarbital depressed blood and brain acetaldehyde levels, but not the acetone levels, in ethanol-treated animals. Pentobarbital and thiopental, alone or with ethanol, had no effect on the blood acetaldehyde levels but increased the brain acetaldehyde levels in ethanol-treated animals. Pentobarbital had no effect on blood acetone or acetaldehyde levels but increased the brain levels of these compounds and, when administered with ethanol, decreased the brain acetone concentration. Thiopental increased the blood acetone level and when administered to ethanol-treated animals decreased the brain acetone levels.