title: (+)-[C-11]-cis-N-benzyl-normetazocine: a selective ligand for sigma receptors in vivo.
abstract: The in vivo biodistribution profile of the novel sigma (sigma) receptor ligand (+)-[C-11]-cis-N-benzyl-normetazocine ([C-11]-(+)-NBnNM) in mouse brain was examined. This radioligand displayed high brain uptake and a distribution consistent with the density of sigma receptors. Brain radioactivity levels peaked at 15 min postinjection and were largely maintained (ca. 80% of maximal values) up to 90 min postinjection. Pretreatment with several different sigma ligands (haloperidol, (+)-pentazocine, DuP 734, ifenprodil) effectively inhibited [C-11]-(+)-NBnNM binding in a dose-dependent manner in all brain regions. [C-11]-(+)-NBnNM binding sites were shown to be saturable with unlabeled (+)-NBnNM (ED50 = 0.02 mg/kg) and enantioselectively inhibited by the optical isomers of pentazocine. A blocking dose of the dopamine D2 antagonist spiperone (1 mg/kg) did not significantly inhibit [C-11]-(+)-NBnNM binding. Pretreatment with the phencyclidine (PCP) blocker 1-[1-(2-thienyl)cyclohexyl] piperidine (TCP) did not significantly alter total brain tissue radioactivity. Thus, [C-11]-(+)-NBnNM binds with high specificity and selectivity to sigma receptors in vivo and offers excellent potential to study sigma receptors in living human brain via positron emission tomography.
authors.affiliation: Division of Nuclear Medicine, Johns Hopkins Medical Institution, Baltimore, MD 21205-2179.
authors.forename: J L
authors.initials: JL
authors.lastname: Musachio
authors.forename: U
authors.initials: U
authors.lastname: Scheffel
authors.forename: M
authors.initials: M
authors.lastname: Stathis
authors.forename: H T
authors.initials: HT
authors.lastname: Ravert
authors.forename: W B
authors.initials: WB
authors.lastname: Mathews
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D006220:Haloperidol / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D008297:Male; D051379:Mice; D009928:Organ Specificity; D010423:Pentazocine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017480:Receptors, sigma / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013134:Spiperone / Q000494:pharmacology; D013237:Stereoisomerism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D008024:Ligands; D010880:Piperidines; D017480:Receptors, sigma; C089049:N-benzylnormetazocine; D013134:Spiperone; C078773:DuP 734; D010622:Phencyclidine; D003496:Cyclazocine; D006220:Haloperidol; D010423:Pentazocine