A bivalent ligand (KDAN-18) containing δ-antagonist and k-agonist pharmacophores bridges δ2 and k1 opioid receptor phenotypes

被引:98
作者
Daniels, DJ [1 ]
Kulkarni, A [1 ]
Xie, ZH [1 ]
Bhushan, RG [1 ]
Portoghese, PS [1 ]
机构
[1] Univ Minnesota, Coll Pharm, Dept Med Chem, Minneapolis, MN 55455 USA
关键词
D O I
10.1021/jm034234f
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
To characterize delta- and kappa-opioid receptor phenotypes, bivalent ligands (KDAN series) containing delta-antagonist (naltrindole) and kappa(1)-agonist (ICI-199,441) pharmacophores were synthesized and evaluated by the intrathecal route using the mouse tail-flick assay and binding studies. The data have suggested that KDAN-18 (2) bridges phenotypic delta(2)- and kappa(1)-receptors. A conceptual model is presented to explain the organizational differences between the opioid receptors that give rise to the phenotypes (delta(1), delta(2), kappa(1), kappa(2)).
引用
收藏
页码:1713 / 1716
页数:4
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