Antinociceptive activity of N-(4-hydroxyphenacetyl)-4-aminoclonidine, a novel analog of clonidine: role of opioid receptors and alpha-adrenoceptors.
N-(4-hydroxyphenacetyl)-4-aminoclonidine, a derivative of the alpha-adrenoceptor agonist p-aminoclonidine, was found to exhibit dose-dependent antinociceptive activity in the mouse writhing assay. In this measure of antinociceptive activity it was less potent than clonidine or xylazine. Naloxone, an opioid receptor antagonist, at a dose sufficient to abolish the antinociceptive activity of morphine, did not affect the antinociceptive activity of N-(4-hydroxyphenacetyl)-4-aminoclonidine, clonidine or xylazine. In contrast, yohimbine, a alpha-adrenoceptor antagonist, reduced the antinociceptive activity of N-(4-hydroxyphenacetyl)-4-aminoclonidine, clonidine and xylazine, but not morphine. The affinity of N-(4-hydroxyphenacetyl)-4-aminoclonidine, clonidine and xylazine for alpha-adrenoceptors in rat aorta was correlated highly with the relative potency for writhing inhibition. These results suggest that the antinociceptive activity of N-(4-hydroxyphenacetyl)-4-aminoclonidine is mediated by alpha-adrenoceptors.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D044482:Benzeneacetamides; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D007700:Kinetics; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D014991:Xylazine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000700:Analgesics; D044482:Benzeneacetamides; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D014991:Xylazine; D015016:Yohimbine; D009270:Naloxone; C029376:hydroxyphenacetyl aminoclonidine; D009020:Morphine; D003000:Clonidine