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Microsomal enzyme induction by methadone and its implications on tolerance to methadone lethality

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Abstract

MANY investigators have sought to explain narcotic tolerance as a result of increased metabolic inactivation of the drug. No evidence for disposition tolerance has yet been reported, however1–6. On the contrary, tolerance to most narcotic effects seems to be adaptive or cellular tolerance, that is a decrease in pharmacological effects even when enough drug is in contact with target cells in the brain to produce marked effects in naive animals7. We wish to report, however, that metabolic inactivation of methadone, a widely used synthetic narcotic, does increase, with a resulting tolerance to its toxic properties.

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Authors and Affiliations

  1. Department of Pharmacology, University of California, San Francisco, California, 94143

    LAWRENCE W. MASTEN, GEORGE R. PETERSON, ALAN BURKHALTER & E. LEONG WAY

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  1. LAWRENCE W. MASTEN
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  2. GEORGE R. PETERSON
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  3. ALAN BURKHALTER
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  4. E. LEONG WAY
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MASTEN, L., PETERSON, G., BURKHALTER, A. et al. Microsomal enzyme induction by methadone and its implications on tolerance to methadone lethality. Nature 253, 200–202 (1975). https://doi.org/10.1038/253200a0

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