Administration of the new COMT inhibitor OR‐611 increases striatal uptake of fluorodopa

Abstract

L‐Dopa is metabolized to 3–O‐methyldopa (3OMD) by catechol‐O‐ methyltransferase (COMT). This reduces the amount of L‐dopa available for entry into brain. We studied the effect of OR‐611, a new COMT inhibitor, on plasma and brain 6‐[18F]‐fluoro‐L‐dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR‐611 pretreatment substantially reduced plasma 6FD metabolism to 3‐O‐methylfluorodopa (3OMFD). PET measurements of striatal 6FD concentrations showed an average 2.3‐fold increase following OR‐611 pretreatment, compared to the same animals in the control state. OR‐611 inhibits plasma metabolism of 6FD and increases brain uptake of this L‐dopa analog. OR‐611 appears to be a promising agent as an adjunct to L‐dopa for the treatment of patients with Parkinson's disease.