Effect of a catechol-O-methyl transferase inhibitor, U-0521, with levodopa administration

  • Fahn S
  • Comi R
  • Snider S
 et al. 
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Abstract

The in vivo effect of 3,4-dihydroxy-2-methyl-propriophenone (U-0521) was studied in rats treated with l-Dopa, 250 mg/kg, intraperitoneally. In a time-course study, experimental animals received two doses of U-0521, 250 mg/kg, i.p., 30 min before l-Dopa and along with l-Dopa. Rats were decapitated at intervals of 30-120 min. U-0521-treated animals showed elevated levels of plasma and brain DOPA and of brain dopamine; they also had a reduction of 3-O-methyldopa (OMD) in plasma and brain, and of homovanillic acid (HVA) in brain, compared to rats treated with l-Dopa alone. A dose-response study of U-0521, given 30 min before l-Dopa, showed that there was effective inhibition of plasma and brain OMD accumulation at a dose of U-0521 of 100 mg/kg, i.p., or greater. Brain HVA accumulation was inhibited at a dose of 200 mg/kg, i.p., or greater. U-0521 can effectively block formation of O-methylated metabolites of l-DOPA and dopamine peripherally and centrally after high dosage l-Dopa administration. © 1979.

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Authors

  • Stanley Fahn

  • Richard Comi

  • Stuart R. Snider

  • A. L.N. Prasad

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