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Journal of Pharmacology And Experimental Therapeutics, Vol. 117, Issue 3, 322-330, 1956
Copyright © 1956 by American Society for Pharmacology and Experimental Therapeutics

THE ENZYMATIC N-DEMETHYLATION OF NARCOTIC DRUGS

Julius Axelrod 1

1 National Institute of Mental Health, National Institutes of Health, Public Health Service, U. S. Department of Health, Education, and Welfare, Bethesda, Maryland

Enzyme systems are described which can N-demethylate a wide variety of narcotic drugs such as morphine and its congeners, methadone and meperidine to their corresponding nor-derivatives and formaldehyde. The enzyme systems are located in the liver microsomes of a number of mammalian species and they require reduced triphosphopyridine nucleotide, oxygen, and other cofactors.

Heat labile factors which inhibit the enzymatic N-demethylation of narcotic drugs have been shown to be present in liver nuclei and mitochondria of the rat but not in the rabbit.

There are marked sex differences in the enzymatic demethylation of narcotic drugs in the rat. Administration of estradiol to male rats results in a decrease in enzyme activity while treatment of female rats with testosterone enhances enzyme activity.

Submitted on March 16, 1956




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Copyright © 1956 by the American Society for Pharmacology and Experimental Therapeutics.