title: [(11)C]-GR89696, a potent kappa opiate receptor radioligand; in vivo binding of the R and S enantiomers.
abstract: The R and S enantiomers of [(11)C]GR89696, [(11)C]-methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl)methyl]-1-piperazinecarboxylate, were synthesized from their appropriate chiral precursors and [(11)C]methyl chloroformate. The [(11)C]-labeled R enantiomer of GR89696, also known as GR103545, demonstrated high affinity in mouse brain with region to cerebellar ratios at 90 minutes of 11.4 and 8.7 for the hypothalamus and olfactory tubercle, respectively. The [(11)C]-labeled S enantiomer showed low affinity and region to cerebellar ratios of 1 for all brain regions. The [(11)C]-labeled GR103545 exhibited a selective and saturable binding for the kappa opioid receptor.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, The Johns Hopkins Medical Institutions, Nelson Building Room B1-151B, 600 North Wolfe Street, Baltimore, MD 21287-0750, USA. htr@jhu.edu
authors.forename: Hayden T
authors.initials: HT
authors.lastname: Ravert
authors.forename: Ursula
authors.initials: U
authors.lastname: Scheffel
authors.forename: William B
authors.initials: WB
authors.lastname: Mathews
authors.forename: John L
authors.initials: JL
authors.lastname: Musachio
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009019:Morphinans / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D000316:Adrenergic alpha-Agonists; D009019:Morphinans; D009292:Narcotic Antagonists; D010879:Piperazines; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C058450:cyprodime; C071609:GR 89696; D009271:Naltrexone; C055382:naltrindole