Identification of the first trans-(3R,4R)-dimethyl-4-(3- hydroxyphenyl)piperidine derivative to possess highly potent and selective opioid kappa receptor antagonist activity
A structurally novel opioid kappa receptor selective
ligand has been identified. This compound, (3R)-7-hydroxy-
(JDTic, 10) demonstrated high affinity for the
kappa receptor in the binding assay (kappa Ki ) 0.3 nM) and highly
potent and selective kappa antagonism in the [35S]GTP-ç-S assay
using cloned opioid receptors (kappa Ki ) 0.006 nM, u/kappa ratio )
570, ä/kappa ratio > 16600).