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Tolerance to morphine effects on renal disposition of xenobiotics in mice

M Garty, A Hurwitz

    The Journal of Pharmacology and Experimental Therapeutics
    |November 1, 1986
    PubMed

    Insights

    Morphine tolerance in mice affects kidney function, reducing its impact on drug elimination. Chronic morphine use diminishes its effects on renal blood flow and tubular function more readily than glomerular filtration.

    Area of Science:

    • Pharmacology
    • Nephrology
    • Toxicology

    Background:

    • Morphine, a potent opioid analgesic, is known to affect renal function.
    • Understanding the development of tolerance to morphine's renal effects is crucial for clinical applications.

    Purpose of the Study:

    • To investigate the development of tolerance to morphine's effects on renal elimination in mice.
    • To differentiate the impact of morphine tolerance on glomerular filtration versus renal blood flow and tubular function.

    Main Methods:

    • Mice received daily morphine injections for 9 days to induce tolerance.
    • Renal clearance of phenol red, p-aminohippurate, and iothalamate was measured in both naive and tolerant mice after acute morphine challenge.
    • Analgesia and hypothermia were assessed to confirm tolerance.

    Main Results:

    • Chronic morphine administration induced tolerance to its analgesic and hypothermic effects.
    • Tolerance was observed in the reduced renal elimination of phenol red and blunted reduction in p-aminohippurate clearance.
    • No significant difference in iothalamate clearance reduction between naive and tolerant mice suggested preserved glomerular filtration.

    Conclusions:

    • Tolerance to morphine's effects on renal blood flow and/or tubular function develops more readily than to its effects on glomerular filtration.
    • The findings suggest that chronic morphine exposure alters renal hemodynamics and tubular handling of substances, contributing to tolerance.

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