title: Nor-binaltorphimine: a potent and selective kappa-opioid receptor antagonist with long-lasting activity in vivo.
abstract: The kappa-receptor selectivity of nor-binaltorphimine (nor-BNI), a highly selective kappa-opioid receptor antagonist in vitro, was examined in vivo by measuring the time course of the antagonistic action of nor-BNI (5 and 20 mg/kg, s.c.) against the responses to U-50488H (10 mg/kg, s.c.), morphine (10 mg/kg, s.c.) and fentanyl (50 micrograms/kg, s.c.) in mice. In the tail pinch test, nor-BNI partially antagonized morphine and fentanyl analgesia, but not U-50488H analgesia in the first 30 min after s.c. administration. However, the kappa-antagonistic action gradually increased, reaching a plateau at 2 hr. This antagonistic action was maintained for at least 4 days. In contrast, the mu-antagonistic action declined to the control level at 2 or 4 hr after nor-BNI administration. In the acetic acid-induced writhing test, nor-BNI also exerted a more potent and selective kappa-antagonistic action at 24 hr than at 1 hr after its s.c. administration. Nor-BNI also showed a long-lasting kappa-antagonism against the hyperthermic response induced by U-50488H (5 mg/kg, s.c.). Thus, we found that nor-BNI is a slow-onset, long-lasting, selective kappa-antagonist in vivo.
authors.affiliation: Basic Research Laboratories, Toray Industries, Inc., Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Endoh
authors.forename: H
authors.initials: H
authors.lastname: Matsuura
authors.forename: C
authors.initials: C
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Nagase
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005283:Fentanyl / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000037:antagonists & inhibitors; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists; D010147:Pain Measurement / Q000187:drug effects; D011759:Pyrrolidines / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa
chemical_list: D000700:Analgesics; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D005283:Fentanyl