(+)-[C-11]-cis-N-benzyl-normetazocine: A selective ligand for sigma receptors in vivo

John L. Musachio, Ursula Scheffel, Marigo Stathis, Hayden T. Ravert, William B. Mathews, Robert F. Dannals

Research output: Contribution to journalArticle

Abstract

The in vivo biodistribution profile of the novel sigma (σ) 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 σ 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 σ 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 σ receptors in vivo and offers excellent potential to study σ receptors in living human brain via positron emission tomography.

LanguageEnglish (US)
JournalLife Sciences
Volume55
Issue number11
DOIs
StatePublished - 1994

Fingerprint

sigma Receptors
Brain
Ligands
Pentazocine
tenocyclidine
Radioactivity
Spiperone
Phencyclidine
Positron emission tomography
Haloperidol
N-benzylnormetazocine
Isomers
Positron-Emission Tomography
Binding Sites
Tissue

Keywords

  • carbon-11
  • positron emission tomography
  • sigma receptors

ASJC Scopus subject areas

  • Pharmacology

Cite this

(+)-[C-11]-cis-N-benzyl-normetazocine : A selective ligand for sigma receptors in vivo. / Musachio, John L.; Scheffel, Ursula; Stathis, Marigo; Ravert, Hayden T.; Mathews, William B.; Dannals, Robert F.

In: Life Sciences, Vol. 55, No. 11, 1994.

Research output: Contribution to journalArticle

Musachio, John L. ; Scheffel, Ursula ; Stathis, Marigo ; Ravert, Hayden T. ; Mathews, William B. ; Dannals, Robert F./ (+)-[C-11]-cis-N-benzyl-normetazocine : A selective ligand for sigma receptors in vivo. In: Life Sciences. 1994 ; Vol. 55, No. 11.
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N2 - The in vivo biodistribution profile of the novel sigma (σ) 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 σ 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 σ 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 σ receptors in vivo and offers excellent potential to study σ receptors in living human brain via positron emission tomography.

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