TY - JOUR
T1 - Antinociceptive activity of N-(4-hydroxyphenacetyl)-4-aminoclonidine, a novel analog of clonidine
T2 - Role of opioid receptors and alpha-adrenoceptors
AU - Hynes, Martin D.
AU - Atlas, Daphne
AU - Ruffolo, Robert R.
PY - 1983/11
Y1 - 1983/11
N2 - 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.
AB - 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.
KW - Alpha-adrenoceptors
KW - Clonidine
KW - Morphine
KW - N-(4-hydroxyphenacetyl)-4-aminoclonidine
KW - Naloxone
KW - Opioid receptors
KW - Xylazine
KW - Yohimbine
UR - http://www.scopus.com/inward/record.url?scp=0021044247&partnerID=8YFLogxK
U2 - 10.1016/0091-3057(83)90097-7
DO - 10.1016/0091-3057(83)90097-7
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C2 - 6316375
AN - SCOPUS:0021044247
SN - 0091-3057
VL - 19
SP - 879
EP - 882
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 5
ER -