(-[C-11]-CIS-N-BENZYL-NORMETAZOCINE - A SELECTIVE LIGAND FOR SIGMA-RECEPTORS IN-VIVO())

The in vivo biodistribution profile of the novel sigma (sigma) recepto r ligand (+)-[C-11]-cis-N-benzyl-normetazocine ([C-11]-(+)-NBnNM) in m ouse brain was examined. This radioligand displayed high brain uptake and a distribution consistent with the density of sigma receptors. Bra in radioactivity levels peaked at 15 min postinjection and were largel y maintained (ca. 80% of maximal values) up to 90 min postinjection. P retreatment with several different sigma ligands (haloperidol, (+)-pen tazocine, DuP 734, ifenprodil) effectively inhibited [C-11]-(+)-NBnNM binding in a dose-dependent manner in all brain regions. [C-11]-(+)-NB nNM binding sites were shown to be saturable with unlabeled (+)-NBnNM (ED50 = 0.02 mg/kg) and enantioselectively inhibited by the optical is omers of pentazocine. A blocking dose of the dopamine D2 antagonist sp iperone (1 mg/kg) did not significantly inhibit [C-ll]-(+)-NBnNM bindi ng. Pretreatment with the phencyclidine (PCP) blocker 1-[1-(2-thienyl) cyclohexyl] piperidine (TCP) did not significantly alter total brain t issue radioactivity. Thus, [C-11]-(+)-NBnNM binds with high specificit y and selectivity to sigma receptors in vivo and offers excellent pote ntial to study sigma receptors in living human brain via positron emis sion tomography.