PT  - JOURNAL ARTICLE
AU  - A. E. Takemori
AU  - G. J. Mannering
TI  - METABOLIC N- AND O-DEMETHYLATION OF MORPHINE- AND MORPHINAN-TYPE ANALGESICS
DP  - 1958 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 171--179
VI  - 123
IP  - 3
4099  - http://jpet.aspetjournals.org/content/123/3/171.short
4100  - http://jpet.aspetjournals.org/content/123/3/171.full
SO  - J Pharmacol Exp Ther1958 Jul 01; 123
AB  - The kinetics of the enzyme reaction(s) found in a mouse liver microsome system responsible for the N- and O-demethylations of morphine- and morphinan-type compounds have been studied. The demethylating capacities of the livers of several species have been investigated. Evidence has been presented to show that the system responsible for the demethylation of narcotic compounds differs from that required for the demethylation of aminoazo dyes, and that N- and O-demethylating systems may also differ. The presence of a free hydroxyl group in the 3-position of both morphine and morphinan compounds retards N-demethylation. The presented studies show that the similarity between the receptors for narcotic action of morphine and morphinan compounds and the receptors for the enzymes that demethylate these compounds is not as great as has been proposed. These observations are discussed as they relate to theories which have been offered picturing the demethylation reaction as a model for the development of tolerance and theories which involve the participation of N-demethylation in the events leading to analgesia.