Properties of TAN-67, a nonpeptide δ-opioid receptor agonist, at cloned human δ-and μ-opioid receptors

Richard J. Knapp, Robert Landsman, Sue Waite, Ewa Malatynska, Eva Varga, Wajujahal Haq, Victor J. Hruby, William R. Roeske, Hiroshi Nagase, Henry I. Yamamura

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

2-methyl-4a α(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a α-octahydro-quinolino[2,3,3-g]isoquinoline (TAN-67) is a nonpeptidic δ-opioid receptor agonist. This report describes its receptor binding affinity and agonist potency at human and mouse δ and μ-opioid receptors. The binding affinities of TAN-67 and the cyclic enkephalin analog, [D-Pen2, 4′-Cl-Phe4, D-Pen5]enkephalin (pCl-DPDPE) were measured by the radioligand binding inhibition studies at mouse and human variants of the δ and μ-opioid receptor using [3H]Naltrindole and [3H]D-Phe-Cys Tyr D Trp Orn Thr Pen-Thr-NH2, respectively. TAN-67 showed high binding affinity (Ki = 0.647 nM) at the human δ-opioid receptor and high δ-opioid receptor binding selectivity (> 1000-fold) relative to the human μ-opioid receptor. TAN-67 also showed high potency (EC50 = 1.72 nM) for the inhibition of forskolin-stimulated cAMP accumulation at human δ-opioid receptors expressed by intact Chinese hamster ovary cells but low potency (EC50 = 1520 nM) at human μ-opioid receptors expressed by intact B82 mouse fibroblast cells. The results show that TAN-67 has similar binding affinities, selectivity and potencies as pCl-DPDPE at human δ and μ-opioid receptors. These results combined with the nonpeptidic structure of TAN-67 suggest that this compound has therapeutic potential as a δ-opioid receptor agonist.

Original languageEnglish (US)
Pages (from-to)129-134
Number of pages6
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume291
Issue number2
DOIs
StatePublished - Oct 15 1995

Keywords

  • Adenylyl cylase
  • Endorphin receptor
  • Radioligand binding
  • Recombinant cell
  • cAMP

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Properties of TAN-67, a nonpeptide δ-opioid receptor agonist, at cloned human δ-and μ-opioid receptors'. Together they form a unique fingerprint.

Cite this