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Research ArticleArticle

CIRCADIAN SYSTEM PHASE-DEPENDENT TOXICITY AND OTHER EFFECTS OF METHOPYRAPONE (SU-4885) IN THE MOUSE

Robert J. Ertel, Franz Halberg and Frank Ungar
Journal of Pharmacology and Experimental Therapeutics December 1964, 146 (3) 395-399;
Robert J. Ertel
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Franz Halberg
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Frank Ungar
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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.

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    • Accepted August 19, 1964.
  • The Williams & Wilkins Comapny

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Journal of Pharmacology and Experimental Therapeutics
Vol. 146, Issue 3
1 Dec 1964
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Research ArticleArticle

CIRCADIAN SYSTEM PHASE-DEPENDENT TOXICITY AND OTHER EFFECTS OF METHOPYRAPONE (SU-4885) IN THE MOUSE

Robert J. Ertel, Franz Halberg and Frank Ungar
Journal of Pharmacology and Experimental Therapeutics December 1, 1964, 146 (3) 395-399;

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Research ArticleArticle

CIRCADIAN SYSTEM PHASE-DEPENDENT TOXICITY AND OTHER EFFECTS OF METHOPYRAPONE (SU-4885) IN THE MOUSE

Robert J. Ertel, Franz Halberg and Frank Ungar
Journal of Pharmacology and Experimental Therapeutics December 1, 1964, 146 (3) 395-399;
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