title: [11C]-methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl)-methyl]-1- piperazinecarboxylate ([11C]GR89696): synthesis and in vivo binding to kappa opiate receptors.
abstract: GR89696, racemic methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl) methyl]-1-piperazinecarboxylate, a kappa opioid receptor ligand, was labeled with [11C]methyl chloroformate. The radiochemical yield was 20% with an observed specific radioactivity of 75.5 GBq/micromol at end of synthesis (2,040 mCi/micromol). Five minutes after intravenous administration, 5.4% of the injected dose accumulated in mouse whole brain. Brain region to cerebellar ratios increased over time with ratios at 90 min of 7.8, 5.6, and 4.5 for the hypothalamus, olfactory tubercle, and striatum, respectively. The uptake of [11C]GR89696 correlated with known kappa opioid receptor densities and was inhibited by kappa opioid selective drugs.
authors.affiliation: Department of Radiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-0750, USA. htr@jhu.edu
authors.forename: H T
authors.initials: HT
authors.lastname: Ravert
authors.forename: W B
authors.initials: WB
authors.lastname: Mathews
authors.forename: J L
authors.initials: JL
authors.lastname: Musachio
authors.forename: U
authors.initials: U
authors.lastname: Scheffel
authors.forename: P
authors.initials: P
authors.lastname: Finley
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
mesh_terms: D000818:Animals; D044482:Benzeneacetamides; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000737:chemistry; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D007553:Isotope Labeling; D007650:Ketanserin / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism* / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism* / Q000493:pharmacokinetics; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D044482:Benzeneacetamides; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D010879:Piperazines; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017473:Receptors, Opioid, kappa; D012702:Serotonin Antagonists; C071609:GR 89696; D013134:Spiperone; D007650:Ketanserin; C045444:U 69593