Catechol-O-methyltransferase inhibition by U-0521 increases striatal utilization of levodopa

  • Avinoam Reches
  • De-hua Jiang
  • Stanley Fahn
Article

Summary

The effects of U-0521, a catechol-O-methyltransferase (COMT) inhibitor, were studied on this enzyme activity and on Dopa metabolism in rat striatum. In vivo maximal inhibition (95%) of COMT activity was obtained at 5 min with enzyme recovery to 64% of basal activity at 120 min. When injected in increasing doses U-0521 (200 mg·kg−1) inhibited, at 10 min, COMT activity by 85% with an IC50=80 mg·kg−1. In rats pretreated with U-0521 and then with DOPA the accumulation of 3-O-methyldopa (OMD) in the plasma was essentially blocked while Dopa, dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) accumulation in the striatum was significantly higher than in DOPA treated controls. U-0521, a potent COMT inhibitor, enhances the availability and utilization of levodopa in the brain and may thus be helpful in future treatment of parkinsonian patients.

Key words

Catechol-O-methyltransferase DOPA Striatum Parkinson's disease 

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Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Avinoam Reches
    • 1
  • De-hua Jiang
    • 1
  • Stanley Fahn
    • 1
  1. 1.Department of Neurology, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA

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