(+)-[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.

Author-supplied keywords

Cite this document ^(BETA)