Section 10
Chapter 9,260

Properties of TAN-67, a nonpeptidic delta-opioid receptor agonist, at cloned human delta- and mu-opioid receptors

Knapp, R.J.; Landsman, R.; Waite, S.; Malatynska, E.; Varga, E.; Haq, W.; Hruby, V.J.; Roeske, W.R.; Nagase, H.; Yamamura, H.I.

European Journal of Pharmacology 291(2): 129-134


ISSN/ISBN: 0014-2999
PMID: 8566162
DOI: 10.1016/0014-2999(95)90088-8
Accession: 009259480

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2-methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha-octahydro-quinolino(2,3,3-g)isoquinoline (TAN-67) is a nonpeptidic delta-opioid receptor agonist. This report describes its receptor binding affinity and agonist potency at human and mouse delta and mu-opioid receptors. The binding affinities of TAN-67 and the cyclic enkephalin analog, (D-Pen-2, 4'-Cl-Phe-4, D-Pen-5)enkephalin (pCl-DPDPE) were measured by radioligand binding inhibition studies at mouse and human variants of the delta and mu-opioid receptor using (3H)Naltrindole and (3H)D-Phe-Cys-Tyr-D-Trp-Irn-Thr-Pen-Thr-NH-2, respectively. TAN-67 showed high binding affinity (K-i = 0.647 nM) at the human delta-opioid receptor and high delta-opioid receptor binding selectivity ( gt 1000-fold) relative to the human mu-opioid receptor. TAN-67 also showed high potency (EC-50 = 1.72 nM) for the inhibition of forskolin-stimulated cAMP accumulation at human delta-opioid receptors expressed by intact Chinese hamster ovary cells but low potency (EC-50 = 1520 nM) at human A-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 delta and mu-opioid receptors. These results combined with the nonpeptidic structure of TAN-67 suggest that this compound has therapeutic potential as a delta-opioid receptor agonist.

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