PMID: 44389Nov 1, 1979

Toxic interaction between narcotic analgesics and inhibitors of catechol-O-methyltransferase

W M DavisJ H Khalsa


A lethal synergism between morphine and tropolone, an inhibitor of catechol-O-methyltransferase, was previously noted in adult male Holtzman rats. The present research demonstrates that this phenomenon generalizes across factors of sex, age, strain (Sprague--Dawley, Wistar) and species (Swiss albino mice). Acute toxicity was also significantly increased (1.5--1.9 times) in the case of codeine, methadone, meperidine and levorphanol, but to a lesser extent than for morphine (4.0 times) in the S-D strain. Another COMT inhibitor, 3,5-dihydroxy-4-methoxybenzoic acid, interacted with morphine in S-D rats to an equal degree as did tropolone. Post-treatment with 1 mg/kg of naloxone in rats or naltrexone in mice reduced the high lethality associated with morphine plus tropolone. There was a pronounced lowering of whole brain norepinephrine (NE) level after morphine plus tropolone in Wistar rats with doses of each component that alone caused no change in NE. Brain dopamine (DA) was elevated by tropolone and by its combination with morphine. Each drug alone caused slight lowering of brain serotonin. Enhancement by tropolone of the toxicity of (+)-amphetamine in mice and rats was of similar magnitude as for morphine. The possible role of b...Continue Reading


Oct 2, 2003·Biological & Pharmaceutical Bulletin·Yasuhiro MoritaYoshihiko Inamori
Apr 13, 2005·Biochemical and Biophysical Research Communications·Ki Suk JeonHo Jeong Kwon


May 17, 1973·Naunyn-Schmiedeberg's Archives of Pharmacology·K ReinholdA Herz
Mar 15, 1974·Nature·A S Schwartz, P L Marchok
Mar 1, 1973·Toxicology and Applied Pharmacology·S Y Yeh, C W Gorodetzky
Jun 1, 1970·Life Sciences. Pt. 1: Physiology and Pharmacology·A S Schwartz, E Eidelberg
Jul 1, 1964·Biochemical Pharmacology·M GOLDSTEINM R MCKEREGHAN
Jan 1, 1962·Journal of Neurochemistry·N KARKIB B BRODIE

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