title: Selective kappa antagonist properties of nor-binaltorphimine in the rat MES seizure model.
abstract: The opioid antagonist properties of nor-binaltorphimine (nor-BNI; 17,17'-Bis(cyclopropylmethyl)-6,6',7,7'-tetradehydro-4,5:4', 5'-diepoxy-6,6'-(imino) [7,7'-bimorphinan]-3,3',14,14'-tetrol) were evaluated in vivo in the rat maximal electroshock (MES) seizure model. Following s.c. or i.c.v. pretreatment, nor-BNI selectively antagonized the anticonvulsant effects of the kappa opioid U50, 488, significantly increasing its ED50 by 2.3 and 4.5 fold, respectively. In contrast, pretreatment with nor-BNI (s.c. or i.c.v.) failed to antagonize the anticonvulsant effects of the selective mu opioid, DAMGO. At the doses and injection routes used, nor-BNI itself had no apparent effect on overt behavior or MES-induced convulsions. These data support the earlier suggestion that the anticonvulsant effects of U50,488 are mediated by kappa opioid receptors and confirm 1) the selectivity of nor-BNI as a kappa antagonist and 2) its applicability as a pharmacological tool in the differentiation of multiple opioid receptors.
authors.affiliation: Department of Medical Neuroscience, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
authors.forename: F C
authors.initials: FC
authors.lastname: Tortella
authors.forename: E
authors.initials: E
authors.lastname: Echevarria
authors.forename: A W
authors.initials: AW
authors.lastname: Lipkowski
authors.forename: A E
authors.initials: AE
authors.lastname: Takemori
authors.forename: P S
authors.initials: PS
authors.lastname: Portoghese
authors.forename: J W
authors.initials: JW
authors.lastname: Holaday
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D000927:Anticonvulsants; D004597:Electroshock; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017473:Receptors, Opioid, kappa; D012640:Seizures / Q000209:etiology / Q000503:physiopathology*
chemical_list: D000927:Anticonvulsants; D004745:Enkephalins; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer