SUPPRESSION BY NUCLEIC ACID- AND PROTEIN-SYNTHESIS INHIBITORS OF DRUG DETOXICATION INDUCED BY SPIRONOLACTONE OR ETHYLESTRENOL

¹ Institut de Médecine et de Chirurgie expérimentales, Université de Montréal

In rats, 24 hours after a single dose of spironolactone or ethylestrenol, the disappearance of pentobarbital from blood is enhanced to a rate in proportion to the decreasing depth of anesthesia. This action is completely suppressed by ribonucleic acid- or protein-synthesis inhibitors such as actinomycin D, puromycin aminonucleoside and cycloheximide, and only partially by 6-mercaptopurine or chloramphenicol. These metabolic inhibitors are incapable in themselves of influencing either the blood concentration of pentobarbital or the depth of anesthesia. The above findings are consistent with the view that induction of drug-metabolizing enzymes is involved in the resistance-increasing effect of spironolactone or ethylestrenol against various compounds.