KAPPA-OPIOID ANTAGONIST EFFECTS OF SYSTEMICALLY ADMINISTERED NOR-BINALTORPHIMINE IN A THERMAL ANTINOCICEPTION ASSAY IN RHESUS-MONKEYS

The effects of subcutaneously administered nor-binaltorphimine (nor-BN I; 1.0 and 3.2 mg/kg) were examined in the warm-water (50-degrees-C an d 55-degrees-C) tail-withdrawal assay in rhesus monkeys (n = 3). Nor-B NI alone produced variable antinociceptive effects in 50-degrees-C wat er up to 3.5 hr after administration but was completely ineffective ag ainst the 55-degrees-C stimulus. Pretreatment with nor-BNI under condi tions where it was devoid of antinociceptive effects produced rightwar d shifts in dose-effect curves for the kappa opioid agonist U50,488 fo r as long as 14 and 21 days after 1.0 and 3.2 mg/kg of nor-BNI, respec tively. Under conditions when U50,488 dose-effect curves were shifted, nor-BNI (3.2 mg/kg) also caused rightward shifts in the antinocicepti ve dose-effect curves of the kappa agonist U69,593 but not in those of the mu agonist alfentanil or the kappa agonists 7,8,beta)]N-methyl-N- [7-(l-pirrolidinyl)l-oxaspiro [4,5)dec-8-yl]4-benzofuranacetamide, bre mazocine, ethylketocyclazocine and Mr2033. It is concluded that under the present conditions, nor-BNI acts as a selective kappa opioid antag onist with an extremely long duration of action. These findings are al so consistent with the notion that nor-BNI may antagonize only compoun ds acting at a subtype of kappa opioid receptor.