Methadone: a potent inhibitor of rat liver aldehyde oxidase.
Several drugs with structural similarities to SKF-525A were tested for their ability to inhibit rat liver aldehyde oxidase using the experimental antitumour agent N-[(2'-dimethylamino)ethyl]acridine-4-carboxamide (AC; NSC 601316; acridine carboxamide) as substrate. The antihistamine D-chlorpheniramine, and the antiarrhythmics disopyramide, procainamide and lignocaine were ineffective in inhibiting this reaction. The antihistamines diphenhydramine, pheniramine, doxylamine, orphenadrine, methapyrilene and pyrilamine, gave IC50 values of 100-500 microM. The narcotic analgesics D-propoxyphene and, in particular, methadone were potent inhibitors of acridine formation with IC50 values of 15.5 and 0.31 microM, respectively. Further analysis indicates mixed non-competitive type inhibition by methadone with inhibition constants (Kis and Kii, respectively) of 0.03 +/- 0.01 (SE) and 0.57 +/- 0.12 microM.
Robertson
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Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, New Zealand.
Gamage
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RS
D000166:Acridines / Q000032:analysis / Q000378:metabolism; D054831:Acridones; D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D011431:Dextropropoxyphene / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008691:Methadone / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology; D051381:Rats
D000166:Acridines; D054831:Acridones; C041300:acridone; D011335:Proadifen; D000445:Aldehyde Oxidoreductases; D042931:Aldehyde Oxidase; D011431:Dextropropoxyphene; D008691:Methadone