Twenty-four hour toxicity rhythms of sedative-hypnotic drugs in mice

Twenty-four hour LD50 values of secobarbital, pentobarbital, phenobarbital, in male Swiss-Webster mice weighing approximately 30 g each. The animals were adapted for three weeks in an environmental room equipped with an automatically-timed photoperiod lasting from 0800 to 2000 h daily. Each mouse was injected intraperitoneally at 6 h time intervals with either phenobarbital or chloral hydrate for toxicity analysis. Secobarbital, pentobarbital and hexobarbital were injected at 3 h time intervals. Peak toxicity was reached at D-0600 with all drugs screened except chloral hydrate which was 180 degrees out of phase. The drugs were least toxic at 1200 h with the exception of chloral hydrate which was least toxic at D-0600 h. These results suggest circadian periodicity in the toxicity of sedative hypnotics. Factors that could be responsible for these variations are discussed.