SB 205607 dihydrobromide

The pharmacological profile of delta opioid receptor ligands, (+) and (-) TAN-67 on pain modulation.[Pubmed:11358331]

Life Sci. 2001 Apr 6;68(19-20):2227-31.

We designed the nonpeptidic highly selective delta opioid receptor agonist on the basis of message address concept and the accessory site theory and synthesized (+/-) TAN-67. In spite of highly potent agonistic activity in in vitro assay, (+/-) TAN-67 (racemate) afforded a weak antinociceptive effect in the mouse tail-flick test. This result led us to separate (+/-) TAN-67 to optical pure compounds, (+) and (-) TAN-67. An i.t.-treatment with (-) TAN-67 produced profound antinociceptive effects through specifically acting on delta1 receptors. Unlike (-) TAN-67, i.t.-administered (+) TAN-67 displayed dose-related nociceptive behaviors such as scratching, biting and licking. The effect of (+) TAN-67 was blocked by i.t.-treatment with NTI (delta receptor antagonist) and (-) TAN-67 (delta1 receptor agonist), but not by morphine (mu receptor agonist). The mechanisms involved in spinal pain modulation induced by (+) and (-) TAN-67 were also described.

Antinociceptive effects of the selective non-peptidic delta-opioid receptor agonist TAN-67 in diabetic mice.[Pubmed:7781682]

Eur J Pharmacol. 1995 Mar 24;276(1-2):131-5.

The antinociceptive potencies of 2-methyl-4 alpha alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12 alpha alpha-octahydro-quinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptidic delta-opioid receptor agonist, were examined using the acetic acid abdominal constriction test and the tail-flick test in diabetic mice. TAN-67, at doses of 3-100 mg/kg, s.c. [corrected], produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal constrictions in both non-diabetic and diabetic mice. The antinociceptive effect of TAN-67 in the acetic acid abdominal constriction test in diabetic mice was greater than that in non-diabetic mice. Indeed, the ED50 (95% confidence limits) value of TAN-67 for the inhibition of acetic acid-induced abdominal constrictions in diabetic mice (6.0 (3.5-10.5) mg/kg) was significantly lower than that in non-diabetic mice (31.4 (14.2-69.4) mg/kg). The antinociceptive effect of TAN-67 was not antagonized by pretreatment with either beta-funaltrexamine, a selective mu-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist. When 7-benzylidenenaltrexone (0.3 mg/kg, s.c.), a selective delta 1-opioid receptor antagonist, was administered 10 min before treatment with TAN-67, the antinociceptive effect of TAN-67 was significantly antagonized. However, naltriben, a selective delta 2-opioid receptor antagonist, had no significant effect on the antinociceptive effect of TAN-67. Furthermore, in the tail-flick test, TAN-67 at doses of 3-30 mg/kg, s.c. [corrected], also produced a marked and dose-dependent antinociceptive effect in diabetic mice, but not in non-diabetic mice. In conclusion, TAN-67 produced an antinociceptive effect through the activation of delta 1-opioid receptors. Furthermore, the results of this study support our hypothesis that mice with diabetes are selectively hyperresponsive to delta 1-opioid receptor-mediated antinociception.

Properties of TAN-67, a nonpeptidic delta-opioid receptor agonist, at cloned human delta- and mu-opioid receptors.[Pubmed:8566162]

Eur J Pharmacol. 1995 Oct 15;291(2):129-34.

2-methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha-octahydro-quinolino[2,3,30g]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-Pen2, 4'-Cl-Phe4, D-Pen5]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-Orn-Thr -Pen-Thr-NH2, respectively. TAN-67 showed high binding affinity (Ki = 0.647 nM) at the human delta-opioid receptor and high delta-opioid receptor binding selectivity ( > 1000-fold) relative to the human mu-opioid receptor. TAN-67 also showed high potency (EC50 = 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 (EC50 = 1520 nM) at human mu-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.