Modification of alpha-adrenoceptor agonist antinociceptive activity by nisoxetine: a selective inhibitor of noradrenergic uptake.
The alpha-adrenoceptor agonists, clonidine and xylazine, produced a dose-dependent antinociceptive effect in the mouse writhing assay as does morphine. Fluoxetine, a highly-specific inhibitor of serotonin uptake, enhanced the antinociceptive effect of morphine in this test but not that of clonidine or xylazine. In contrast, nisoxetine, a selective inhibitor of noradrenergic uptake, significantly potentiated the antinociceptive activity of morphine, clonidine, and xylazine. These findings strengthen the evidence for an involvement of a noradrenergic mechanism in the antinociceptive effects of alpha-adrenoceptor agonists.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000700:Analgesics; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology*; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D011437:Propylamines / Q000494:pharmacology*; D014991:Xylazine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D011437:Propylamines; D005473:Fluoxetine; C011386:nisoxetine; D014991:Xylazine; D003000:Clonidine; D009638:Norepinephrine