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From the Brookhaven National Laboratory (Drs. Fowler, Volkow, Logan, Schlyer, Wang, Wolf, and Gatley, and R. MacGregor, N. Pappas, D. Alexoff, and C. Shea), Upton, NY; Hoffmann-La Roche Inc. (Drs. Dorflinger and Yoo and L. Morawsky), Nutley, NJ; and New York University (Dr. Fazzini), New York, NY.
The possibility of slowing the progression of Parkinson's disease (PD) with inhibitors of monoamine oxidase B (MAO B) has stimulated the development of new MAO B inhibitor drugs. Ro 19 6327 is a highly selective inhibitor of MAO B currently under clinical investigation. We used positron emission tomography (PET) and the MAO B tracer [11C] L-deprenyl to determine the degree and reversibility of human brain MAO B inhibition by Ro 19 6327 in six early Parkinson's disease patients who were treated with different doses of Ro 19 6327 (25 mg [n = 3], 50 mg [n = 2], and 100 mg [n = 1]; 0.34 to 1.4 mg/kg) every 12 hours for 1 week. Each patient had three PET scans to assess baseline MAO B activity, degree of trough inhibition, and reversibility. A control group of four elderly normal subjects was scanned twice to assess reproducibility of repeated measures. Four of the patients showed reduction of MAO B concentration to 1% to 7% of baseline on doses of 0.43 mg/kg or greater, and the remaining two at 0.34 mg/kg showed significant but incomplete inhibition (10% to 21% of baseline in the global region and in the thalamus, basal ganglia, and mesencephalon). Thus, 0.4 mg/kg or greater of Ro 19 6327 given every 12 hours is the minimum dose necessary to provide >90% inhibition of brain MAO B in patients with early PD. Brain MAO B activity returned to baseline values by 36 hours after drug discontinuation.
Address correspondence and reprint requests to Dr. Joanna S. Fowler, Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973.
This research was carried out at Brookhaven National Laboratory under contract DE-AC02-76H00016 with the US Department of Energy and supported by its Office of Health and Environmental Research, and also by Hoffmann-La Roche Inc., Nutley, NJ, and National Institutes of Health grants NS 15638 and NS 15380.
Received September 9, 1992. Accepted for publication in final form February 4, 1993.
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