Effect of Nitecapone (OR-462) on the Pharmacokinetics of Levodopa and 3-O-Methyldopa Formation in Cynomolgus Monkeys
- 1 December 1990
- journal article
- review article
- Published by Wolters Kluwer Health in Clinical Neuropharmacology
- Vol. 13 (6), 544-552
- https://doi.org/10.1097/00002826-199012000-00006
Abstract
Summary 3-O-Methyldopa (OMD) is the principal circulating metabolite formed from exogenously administered levodopa. We studied the effect of nitecapone (OR-462), a novel inhibitor of catechol-O-methyltransferase (COMT), on OMD formation in cynomolgus monkeys following intravenous levodopa administration. The drug does not cross the blood-brain barrier, and therefore inhibits only peripheral OMD formation. At a dose of 5 mg/kg, nitecapone reduced the area under the OMD concentration-time curve by 50%. Inhibition of OMD production was maximal at 65% following a dose of 10 mg/kg. A dose of 15 mg/kg produced no further inhibition. The plasma pharmacokinetics of carbidopa, levodopa, and OMD in the monkeys were similar to those in humans. No adverse physiological effects of nitecapone were observed. In single-dose studies, OR-462 is an effective peripheral COMT inhibitor.Keywords
This publication has 12 references indexed in Scilit:
- Inhibition of catechol-O-methyltransferase activity by two novel disubstituted catechols in the ratEuropean Journal of Pharmacology, 1988
- Clinical significance of the relationship between O‐methyldopa levels and levodopa intakeNeurology, 1988
- Catechol-O-methyltransferase activity in human and rat small intestineLife Sciences, 1988
- Controlled‐release levodopa/carbidopa.Neurology, 1987
- 3‐O‐Methyldopa and the response to levodopa in Parkinson's diseaseAnnals of Neurology, 1987
- 3–0‐methyldopa and motor fluctuations in Parkinson's diseaseNeurology, 1987
- Effects of l‐DOPA on the Concentrations of Free and Sulfoconjugated Cathecholamines in Plasma, Cerebrospinal Fluid, Urine, and Central and Peripheral Nervous System Tissues of the RatJournal of Neurochemistry, 1985
- Effects of 3‐OM‐dopa on monoarnine metabolism in rat brainNeurology, 1983
- 3‐O‐Methyldopa inhibits rotations induced by levodopa in rats after unilateral destruction of the nigrostriatal pathwayNeurology, 1982
- Catechol-O-methyltransferase activity: A determinant of levodopa responseClinical Pharmacology & Therapeutics, 1980