title: Monoamine oxidase B (MAO B) inhibitor therapy in Parkinson's disease: the degree and reversibility of human brain MAO B inhibition by Ro 19 6327.
abstract: 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.
authors.affiliation: Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973.
authors.forename: J S
authors.initials: JS
authors.lastname: Fowler
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.forename: J
authors.initials: J
authors.lastname: Logan
authors.forename: D J
authors.initials: DJ
authors.lastname: Schlyer
authors.forename: R R
authors.initials: RR
authors.lastname: MacGregor
authors.forename: G J
authors.initials: GJ
authors.lastname: Wang
authors.forename: A P
authors.initials: AP
authors.lastname: Wolf
authors.forename: N
authors.initials: N
authors.lastname: Pappas
authors.forename: D
authors.initials: D
authors.lastname: Alexoff
authors.forename: C
authors.initials: C
authors.lastname: Shea
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D010848:Picolinic Acids / Q000627:therapeutic use*; D012016:Reference Values; D012642:Selegiline; D014055:Tomography, Emission-Computed
chemical_list: D000978:Antiparkinson Agents; D002250:Carbon Radioisotopes; D010848:Picolinic Acids; D012642:Selegiline; C059303:lazabemide; D008995:Monoamine Oxidase