A bivalent ligand (KDAN-18) containing delta-antagonist and kappa-agonist pharmacophores bridges delta2 and kappa1 opioid receptor phenotypes.
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)).
Daniels
David J
DJ
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Kulkarni
Amol
A
Xie
Zhihua
Z
Bhushan
Rashmi G
RG
Portoghese
Philip S
PS
D000494:Allosteric Regulation; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D006801:Humans; D007278:Injections, Spinal; D008024:Ligands; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010641:Phenotype; D011759:Pyrrolidines / Q000737:chemistry; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013329:Structure-Activity Relationship
D000577:Amides; C500055:KDAN 18; D008024:Ligands; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; C058468:ICI 199441; D009271:Naltrexone; C055382:naltrindole