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Updated: Jul 16, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Kappa receptor bivalent ligands
1Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, Massachusetts 02478, USA.
Abstract:
Bivalent ligands of kappa opioid agonists and antagonists, such as norBNI and BNI, are used as tools to elucidate the kappa 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 kappa/micro or mixed kappa/delta 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 kappa antagonist (JDTic) provides an additional tool to characterize kappa opioid receptor.
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