title: Dopamine D1 agonist R-[11C]SKF 82957: synthesis and in vivo characterization in rats.
abstract: The active enantiomer R-SKF 82957 was labeled with 11C by N-[11C]methylation of the full dopamine (D1) agonist R-SKF 81297, using [11C]methyl iodide in the presence of N-ethyldiisopropylamine, in high specific activity, radiochemical purity and yields. Compared with the D1 agonist R/S-[11C]SKF 82957, R-[11C]SKF 82957 showed higher binding in the D1 rich regions, such as striatum and olfactory tubercles (approximately 1.7 times), thereby improving the tissue contrast. R-[11C]SKF 82957 exhibited high in vivo binding selectivity for D1 receptors in rats, because only high doses of D1 competitors, but not D2 or serotonin (5-HT2) blockers, significantly reduced the radioactivity levels in all brain areas. No labeled metabolites were detected in rat brain. These results indicate that R-[11C]SKF 82957 will provide more sensitive measurements of D1 receptors in in vivo studies than the racemic mixture.
authors.affiliation: Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Ontario, Canada. jdasilva@clarke-inst.on.ca
authors.forename: J N
authors.initials: JN
authors.lastname: DaSilva
authors.forename: R A
authors.initials: RA
authors.lastname: Schwartz
authors.forename: E R
authors.initials: ER
authors.lastname: Greenwald
authors.forename: C M
authors.initials: CM
authors.lastname: Lourenco
authors.forename: A A
authors.initials: AA
authors.lastname: Wilson
authors.forename: S
authors.initials: S
authors.lastname: Houle
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D001552:Benzazepines; D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; C099238:SKF 82957