Binaltorphimine and nor-binaltorphimine, potent and selective kappa-opioid receptor antagonists.

The opioid antagonist activities of two bivalent ligands, BNI and nor-BNI, have been evaluated in smooth muscle preparations and in mice. Both ligands are highly potent and selective as kappa opioid receptor antagonists, with relatively feeble blocking activity at mu and delta opioid receptors. BNI and nor-BNI represent the first highly selective kappa opioid receptor antagonists and should be of great utility as molecular probes for identifying the interaction of agonist ligands with kappa opioid receptors in vitro and in vivo.