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  • Title: Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.
    Author: Guttman M, Léger G, Reches A, Evans A, Kuwabara H, Cedarbaum JM, Gjedde A.
    Journal: Mov Disord; 1993 Jul; 8(3):298-304. PubMed ID: 8341294.
    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.
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