THE INHIBITION OF THE LIVER MICROSOMAL N-DEMETHYLATION OF MORPHINE AND T.2636 BY N-ALLYL NORMOPHINE AND ITS PHARMACOLOGICAL IMPLICATIONS
Abstract
Theories of the pharmacological action of morphine imply that the N-demethylation of morphine by liver microsomal enzymes should be competitively inhibited by N-allyl normorphine (Nalorphine). These have been challenged on the grounds that Nalorphine is a non-competitive inhibitor. Inhibition of morphine and T2636 N-demethylation by Nalorphine has been investigated using rat liver microsomes and it appeared, from the application of the method of Lineweaver and Burk, to be neither competitive nor noncompetitive but a mixture of the two. Nalorphine was shown to be metabolized approximately twice as fast as morphine by the same microsomal preparations, i.e. in the inhibition studies the inhibitor concentration was not constant, hence the simple Michaelis-Menton theory (on which the method of Lineweaver and Burk is based) cannot be applied to this system. It is concluded that this type of experiment may be used neither to support nor challenge hypotheses of the pharmacological activity of morphine.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 16, 1964
- Accession Number
- AD0355396
Entities
People
- D. R. Davies
- L. Leadbeater