Reduction of circulating 3-O-methyldopa by inhibition of catechol-O-methyltransferase with OR-611 and OR-462 in cynomolgus monkeys: implications for the treatment of Parkinson's disease.

Abstract

We studied the effectiveness of OR-611 and OR-462, two novel inhibitors of the enzyme catechol-O-methyltransferase (COMT), on 3-O-methyldopa (OMD) formation in cynomolgus monkeys following intravenous levodopa administration. OR-611 dose-dependently reduced the area under the OMD concentration-vs-time curve, reduced maximum plasma OMD concentrations, delayed the time to peak OMD levels, reduced systemic levodopa clearance, and prolonged the elimination half-life of levodopa. Similar effects on peripheral levodopa metabolism were seen with doses of 15 mg/kg of OR-611 and OR-462, its sister compound, which lacks the ability to penetrate the central nervous system (CNS).

• Authors: J M Cedarbaum, G Leger, M Guttman
• Journal: Clinical neuropharmacology (Clin Neuropharmacol) Vol. 14 Issue 4 Pg. 330-42 (Aug 1991) ISSN: 0362-5664 [Print] United States
• PMID: 1913700 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catechol O-Methyltransferase Inhibitors
• Catechols
• Nitriles
• Pentanones
• Tyrosine
• Levodopa
• entacapone
• nitecapone
• 3-methoxytyrosine

Topics

• Animals
• Catechol O-Methyltransferase Inhibitors
• Catechols (pharmacokinetics, pharmacology)
• Levodopa (blood, metabolism)
• Macaca fascicularis
• Male
• Nitriles
• Parkinson Disease (drug therapy, metabolism)
• Pentanones (pharmacokinetics, pharmacology)
• Tyrosine (analogs & derivatives, biosynthesis, blood, metabolism)