title: Synthesis of [11C-methyl]-(-)-OSU6162, its regional brain distribution and some pharmacological effects of (-)-OSU6162 on the dopaminergic system studied in the rhesus monkey by positron emission tomography.
abstract: The labelling of the presynaptic dopamine receptor antagonist (-)-OSU6162, ((S)-(-)-3-(3-(methylsulfonyl)phenyl)-1-propylpiperidine) was performed by an alkylation with [11C]methyl iodide of the thio anion (-)-OSU1281, followed by a selective oxidation to the corresponding methyl sulfone, [11C-methyl]-(-)-OSU6162. The total radiochemical yield calculated from the produced [11C]carbon dioxide to final product was about 25% and the time of synthesis was in the range of 40 min from end of bombardment. The synthesis of the precursor, (-)-OSU1281, was performed from (-)-3PPP in a three-step synthesis. The regional brain distribution of (-)-OSU6162 radiolabelled with 11C was studied in rhesus monkeys by means of positron emission tomography, PET. [11C-Methyl]-(-)-OSU6162 was rapidly and uniformly distributed to gray matters of the brain, and no decrease of radioactivity uptake in the brain was seen after pretreatment with 1 to 3 mg/kg/h of (-)-OSU6162. The effect of doses of 1 to 3 mg/kg/h of (-)-OSU6162 on the dopamine binding was studied by PET using [11C-methyl]raclopride. Radioactivity in the striatum was significantly and dose-dependently decreased by (-)-OSU6162 (r = 0.88), supporting competition with dopamine for selective binding to dopamine receptors.
authors.affiliation: Uppsala University Pet Centre, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Neu
authors.forename: P
authors.initials: P
authors.lastname: Hartvig
authors.forename: R
authors.initials: R
authors.lastname: Torstenson
authors.forename: K J
authors.initials: KJ
authors.lastname: Fasth
authors.forename: C
authors.initials: C
authors.lastname: Sonesson
authors.forename: N
authors.initials: N
authors.lastname: Waters
authors.forename: A
authors.initials: A
authors.lastname: Carlsson
authors.forename: J
authors.initials: J
authors.lastname: Tedroff
authors.forename: B
authors.initials: B
authors.lastname: Långström
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D008253:Macaca mulatta; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D020891:Raclopride; D012457:Salicylamides / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D010880:Piperidines; D012457:Salicylamides; C109513:OSU 6162; D020891:Raclopride; D004298:Dopamine