The effects of subcutaneously administered nor-binaltorphimine (nor-BNI; 1.0 and 3.2 mg/kg) were examined in the warm-water (50°C and 55°C) tail- withdrawal assay in rhesus monkeys (n = 3). Nor-BNI alone produced variable antinociceptive effects in 50°C water up to 3.5 hr after administration but was completely ineffective against the 55°C stimulus. Pretreatment with nor- BNI under conditions where it was devoid of antinociceptive effects produced rightward shifts in dose-effect curves for the kappa opioid agonist U50,488 for as long as 14 and 21 days after 1.0 and 3.2 mg/kg of nor-BNI, respectively. Under conditions when U50,488 dose-effect curves were shifted, nor-BNI (3.2 mg/kg) also caused rightward shifts in the antinociceptive dose- effect curves of the kappa agonist U69,593 but not in those of the μ agonist alfentanil or the kappa agonists [5R-(5,7,8,β)]N-methyl-N-[7-(1- pirrolidinyl)1-oxaspiro [4,5]dec-8-yl]4-benzofuranacetamide, bremazocine, ethylketocyclazocine and Mr2033. It is concluded that under the present conditions, nor-BNI acts as a selective kappa opioid antagonist with an extremely long duration of action. These findings are also consistent with the notion that nor-BNI may antagonize only compounds acting at a subtype of kappa opioid receptor.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1993|
ASJC Scopus subject areas
- Molecular Medicine