Abstract

Blood corticosterone levels in Bagg albino and certain hybrid mice are greatly depressed by 20 mg/kg of methopyrapone (SU-4885) at 20 minutes postinjection. Doses higher than 200 mg/kg produced a general anesthesia and doses from 300 to 400 mg/kg of SU-4885 were lethal in several strains of mice. Moreover, three toxicity experiments, carried out by indirect periodicity analysis, revealed a statistically significant circadian rhythm in the susceptibility of the male C or CD₂D₂ mouse to the early lethal effects of SU-4885.

Under appropriately standardized conditions the number of deaths occurring within 6 hours after the injection of SU-4885 (into separate groups of comparable mice injected at 4-hour intervals during 24-hour periods) depended upon the circadian system phase at the time of drug administration.

The amplitude of this circadian susceptibility-resistance cycle to SU-4885 was large, involving under certain conditions, changes of over 50% around the mean. As to its external timing, the circadian rhythmic increase in susceptibility to methopyrapone occurred prior to the beginning of the daily dark period in mice kept on a regimen of 12 hours of light alternating with 12 hours of darkness. The findings extend the scope of circadian system analysis in the study of respouses to drugs.