ADMINISTRATION OF THE NEW COMT INHIBITOR OR-611 INCREASES STRIATAL UPTAKE OF FLUORODOPA

L-Dopa is metabolized to 3-O-methyldopa (3OMD) by catechol-O-methyltra nsferase (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-[F-18]-fluoro-L-dopa (6FD) metabolism in cynomolgu s monkeys with positron emission tomography (PET). OR-611 pretreatment substantially reduced plasma 6FD metabolism to 3-O-methyltluorodopa ( 3OMFD). PET measurements of striatal 6FD concentrations showed an aver age 2.3-fold increase following OR-611 pretreatment, compared to the s ame 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 p atients with Parkinson's disease.