A Bivalent Ligand (KDAN-18) Containing δ-Antagonist and κ-Agonist Pharmacophores Bridges δ<sub>2</sub> and κ<sub>1</sub> Opioid Receptor Phenotypes<sup>†</sup> DanielsDavid J. KulkarniAmol XieZhihua BhushanRashmi G. PortoghesePhilip S. 2005 To characterize δ- and κ-opioid receptor phenotypes, bivalent ligands (KDAN series) containing δ-antagonist (naltrindole) and <i>κ</i><sub>1</sub>-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 (<b>2</b>) bridges phenotypic δ<sub>2</sub>- and κ<sub>1</sub>-receptors. A conceptual model is presented to explain the organizational differences between the opioid receptors that give rise to the phenotypes (δ<sub>1</sub>, δ<sub>2</sub>, κ<sub>1</sub>, κ<sub>2</sub>).