nor-Binaltorphimine

nor-Binaltorphimine (Norbinaltorphimine; NorBNI) is a selective, long-acting competitive antagonist of the κ-opioid receptor. nor-Binaltorphimine blocks κ-opioid receptor-mediated analgesic effects, and inhibits butorphanol-induced changes in κ-opioid receptor binding kinetics, desensitization and down-regulation. nor-Binaltorphimine suppresses specific opioid withdrawal symptoms, precipitates withdrawal behaviors in butorphanol-dependent rats, and serves as a molecular probe for studying κ-opioid receptor-agonist interactions. nor-Binaltorphimine is applicable to research related to neurological disorders such as pain^[1][2][3]. In Vitro:Nor-binaltorphimine (0.01 nM-0.1 μM; 120 min) displaces the binding of [³H]U-69,593 to κ-opioid receptors in rat cortical cell membranes. Its K_i value is 4.8 nM in saline-infused rats, while its potency increases 12-fold (K_i = 0.4 nM) in butorphanol-infused rats, indicating that κ-opioid receptors are hypersensitive to this antagonist^[2].
nor-Binaltorphimine (20-200 nM; 30 min) potently antagonizes κ-selective agonists in the longitudinal muscle of guinea pig ileum, while it exhibits extremely weak antagonistic effects on the μ-selective agonist morphine, with a κ/μ selectivity ratio of 19.2^[3].
nor-Binaltorphimine (20 nM; 30 min) potently antagonizes κ-selective agonists in rabbit vas deferens preparations^[3]. In Vivo:Nor-binaltorphimine (30 μg; intracerebroventricular injection; single administration / twice daily; consecutive 10 days) acts as a selective, long-acting κ-opioid receptor antagonist in rats^[1].
Nor-binaltorphimine (12-100 nM/5 μl; intracerebroventricular injection; administered twice, at 3 hours before and 48 hours after the initiation of butorphanol infusion) blocks most naloxone-precipitated withdrawal symptoms in butorphanol-dependent rats, exerts a significant blocking effect on diarrhea, alleviates forepaw tremor, and prevents butorphanol-induced desensitization of κ-opioid receptors in the cortex and striatum, as well as receptor downregulation in the cortex^[2].