Assuntos
Antiparkinsonianos/uso terapêutico , Nefropatias/induzido quimicamente , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/farmacocinética , Carbidopa/efeitos adversos , Carbidopa/farmacocinética , Carbidopa/uso terapêutico , Catecol O-Metiltransferase/efeitos adversos , Catecol O-Metiltransferase/farmacocinética , Catecol O-Metiltransferase/uso terapêutico , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/farmacocinética , Agonistas de Dopamina/uso terapêutico , Humanos , Nefropatias/metabolismo , Levodopa/efeitos adversos , Levodopa/farmacocinética , Levodopa/uso terapêutico , Inibidores da Monoaminoxidase/efeitos adversos , Inibidores da Monoaminoxidase/farmacocinética , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/metabolismoRESUMO
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.