Extremely long-lasting antagonistic actions of nor-binaltorphimine (nor-BNI) in the mouse tail-flick test.
The duration of antagonistic action of nor-binaltorphimine (nor-BNI), a kappa antagonist, of antinociception resulting from selective opioid agonists, was examined using the mouse tail-flick assay as the endpoint. Nor-BNI (1 nmol, i.c.v. at -20 min) antagonized equiantinociceptive doses of the opioid kappa agonists (5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro (4,5)dec-8-yl) benzeneacetamide (U69,593) (70 nmol i.c.v.) or bremazocine (25 nmol i.c.v.), but did not antagonize antinociception produced by the mu opioid-selective [D-Ala2, NMePhe4, Gly-ol]enkephalin or the delta opioid-selective [D-Pen2, D-Pen5]enkephalin. Pretreatment with nor-BNI (1 nmol i.c.v.) antagonized the antinociceptive effects of U69,593 and bremazocine for up to 28 days. At all pretreatment times, the antinociceptive dose-response lines for these kappa agonists were displaced to the right to various degrees in a parallel fashion; an increasing rightward displacement of the U69,593 and bremazocine antinociceptive dose-response lines was observed at 1 and 3 days after a single nor-BNI pretreatment, with a gradual return toward the control level at later times after pretreatment. Increasing the dose of nor-BNI to 10 nmol produced only a transient blockade of equiantinociceptive doses of the mu selective agonist [D-Ala2, NMePhe4, Gly-ol]enkephalin and the delta selective agonist [D-Pen2, D-Pen5]enkephalin (at 20-30 min post-nor-BNI pretreatment).(ABSTRACT TRUNCATED AT 250 WORDS)
Horan
P
P
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson.
Taylor
J
J
Yamamura
H I
HI
Porreca
F
F
D000367:Age Factors; D000818:Animals; D044482:Benzeneacetamides; D001575:Benzomorphans / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011759:Pyrrolidines / Q000037:antagonists & inhibitors / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa; D013997:Time Factors
D044482:Benzeneacetamides; D001575:Benzomorphans; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; C027248:bremazocine; C045444:U 69593