Interactions of paraldehyde with ethanol and chloral hydrate

The interaction of the depressant and toxic actions of paraldehyde with those of ethanol and chloral hydrate were investigated in two strains of male mice by determination of the ED50 for anesthetic action (righting reflex loss) and the 24 hr LD50, respectively. In all instances less than simple additive synergism was observed. Onset and duration times for the anesthetic actions of paraldehyde and ethanol were observed to be almost identical. Investigation of the time of maximum toxic effect revealed paraldehyde itself and mixtures containing 40% or more paraldehyde to be more acutely toxic than ethanol or mixtures containing more than 80% ethanol, suggesting the possibility of different mechanism of toxic action as contributory reasons for the less than simple additivity of the lethal effects of these two agents. The onset and duration of the anesthetic effect of chloral hydrate was longer than that of equipotent doses of paraldehyde, binary mixtures of these two agents having intermediate onset times but much longer duration than either compound, leading to the conclusion the less than simple additivity observed with respect to both the depressant and toxic actions of paraldehyde and chloral hydrate resulted from different time courses of action.