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Related Experiment Videos

Glucuronidation of apomorphine.

R S El-Bachá1, S Leclerc, P Netter

  • 1UMR CNRS-Université Henri Poincaré-Nancy 1 N 7561, laoratoire de Pharmacologie, Faculté de Médecine, Vandoeuvre-lès-Nancy, France.

Life Sciences
|October 6, 2000
PubMed
Summary
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Apomorphine, used for Parkinson's disease, is glucuronidated in rat liver by UGT2B1. This study confirms apomorphine is not significantly glucuronidated in rat brain microsomes.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Drug Metabolism

Background:

  • Apomorphine is a key drug in Parkinson's disease therapy.
  • Understanding its metabolism, specifically glucuronidation, is crucial for drug efficacy and safety.
  • Catechol metabolism involves conjugation by uridine-diphosphate glucuronosyltransferases (UGTs).

Purpose of the Study:

  • To characterize the glucuronidation of apomorphine in rat liver and brain microsomes.
  • To identify the specific UGT isoforms responsible for apomorphine glucuronidation.
  • To investigate the role of UGTs in the metabolism of other catechols.

Main Methods:

  • Incubation of rat liver and brain microsomes with UDP-[U-14C]glucuronic acid.
  • Separation and identification of glucuronides using thin-layer chromatography and high-pressure liquid chromatography.

Related Experiment Videos

  • Mass spectrometry analysis to confirm glucuronide structures.
  • Assay of apomorphine glucuronidation using recombinant UGT1A6 and UGT2B1 isoforms.

    • Main Results:

    • Rat liver microsomes efficiently glucuronidated apomorphine, forming two monoglucuronides.
    • 4-nitrocatechol was the most efficiently conjugated catechol in liver microsomes.
    • Only 4-nitrocatechol, not apomorphine, was significantly glucuronidated in rat brain microsomes.
    • Recombinant UGT2B1, but not UGT1A6, significantly catalyzed apomorphine glucuronidation.

    Conclusions:

    • Apomorphine glucuronidation in rat liver is primarily mediated by the UGT2B1 isoform.
    • The absence of significant apomorphine glucuronidation in rat brain microsomes suggests limited central metabolism.
    • These findings contribute to understanding apomorphine's pharmacokinetic profile and potential drug interactions.