PT  - JOURNAL ARTICLE
AU  - E R Butelman
AU  - S S Negus
AU  - Y Ai
AU  - B R de Costa
AU  - J H Woods
TI  - Kappa opioid antagonist effects of systemically administered nor-binaltorphimine in a thermal antinociception assay in rhesus monkeys.
DP  - 1993 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1269--1276
VI  - 267
IP  - 3
4099  - http://jpet.aspetjournals.org/content/267/3/1269.short
4100  - http://jpet.aspetjournals.org/content/267/3/1269.full
SO  - J Pharmacol Exp Ther1993 Dec 01; 267
AB  - The effects of subcutaneously administered nor-binaltorphimine (nor-BNI; 1.0 and 3.2 mg/kg) were examined in the warm-water (50 degrees C and 55 degrees C) tail-withdrawal assay in rhesus monkeys (n = 3). Nor-BNI alone produced variable antinociceptive effects in 50 degrees C water up to 3.5 hr after administration but was completely ineffective against the 55 degrees 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 mu agonist alfentanil or the kappa agonists [5R-(5,7,8,beta)]N-methyl-N-[7- (1-pirrolidinyl)1-oxaspiro[4,5]dec-8-yl]4-benzofuranaceta mide, 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.