Kappa Receptor Bivalent Ligands

Bivalent ligands of κ opioid agonists and antagonists, such as norBNI and BNI, are used as tools to elucidate the κ receptor characteristics. Bivalent ligands may also be effective analgesics although none have this far been used clinically. Structure-activity relationships (SAR) and molecular modeling led to the development of a more potent and selective kappa antagonist (5'-guanidinylnaltrindole, GNTI). Novel homo and hetero bivalent ligands with high mixed κ/μ or mixed κ/δ affinity and intriguing pharmacological properties may eventually lead to useful analgesics with fewer adverse side effects. Bivalent ligands were also developed that could act as probes of the receptor-oligomerzation and organization phenomena. A structurally unique κ antagonist (JDTic) provides an additional tool to characterize κ opioid receptor.