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Morphine metabolism in mouse brain.

A Wahlström1, L Hammar, L G Lundin

  • 1Div. of Clinical Pharmacology, University Hospital, Uppsala, Sweden.

NIDA Research Monograph
|January 1, 1986
PubMed
Summary
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Morphine glucuronidation activity varies in mouse brains. The DBA strain showed significantly higher morphine-3-glucuronide formation rates than the C57BL strain.

Area of Science:

  • Pharmacogenetics
  • Neuroscience
  • Drug Metabolism

Background:

  • UDP-glucuronosyltransferases (UGTs) are crucial enzymes in drug metabolism.
  • Genetic variations in UGTs can influence drug efficacy and toxicity.
  • Brain UGT activity plays a role in the central effects of drugs like morphine.

Purpose of the Study:

  • To investigate morphine UDP-glucuronyltransferase (UGT) activity in the brains of BXD recombinant inbred mice.
  • To identify potential genetic influences on morphine metabolism within the central nervous system.

Main Methods:

  • Assessing UDP-glucuronyltransferase activity in brain homogenates from BXD mice.
  • Quantifying the formation rate of morphine-3-glucuronide (M3G).
  • Comparing enzyme activity between progenitor strains (DBA/2J and C57BL/6J) and their derived BXD strains.

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Main Results:

  • Morphine UDP-glucuronyltransferase activity was successfully demonstrated in the mouse brain.
  • The formation rate of morphine-3-glucuronide was approximately fourfold higher in the DBA progenitor strain compared to the C57BL progenitor strain.
  • This suggests significant genetic variability in brain morphine metabolism among BXD strains.

Conclusions:

  • Brain morphine glucuronidation exhibits strain-dependent differences in mice.
  • Genetic factors significantly influence the metabolic capacity of morphine in the central nervous system.
  • These findings have implications for understanding individual responses to opioid analgesics.