Selective kappa antagonist properties of nor-binaltorphimine in the rat mes seizure model

The opioid antagonist properties of nor-binaltorphimine (nor-BNI; 17,17′-Bis (cyclopropylethyl)-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.