A bivalent ligand (KDAN-18) containing delta-antagonist and kappa-agonist pharmacophores bridges delta2 and kappa1 opioid receptor phenotypes

J Med Chem. 2005 Mar 24;48(6):1713-6. doi: 10.1021/jm034234f.

Abstract

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)).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allosteric Regulation
  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology
  • Animals
  • Binding, Competitive
  • Cell Line
  • Humans
  • Injections, Spinal
  • Ligands
  • Mice
  • Naltrexone / analogs & derivatives*
  • Naltrexone / chemical synthesis*
  • Naltrexone / chemistry
  • Naltrexone / pharmacology
  • Phenotype
  • Pyrrolidines / chemistry
  • Radioligand Assay
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Receptors, Opioid, kappa / agonists*
  • Structure-Activity Relationship

Substances

  • Amides
  • KDAN 18
  • Ligands
  • Pyrrolidines
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • ICI 199441
  • Naltrexone
  • naltrindole