Antagonism of the antinociceptive action of xylazine, an α-sympathomimetic agent, by adrenoceptor and cholinoceptor blocking agents

Abstract

The potency of adrenoceptor and cholinoceptor agents to antagonize the antinociceptive action of xylazine, an α-sympathomimetic agent, was studied. Yohimbine (1–2 mg/kg) and piperoxan (2.5–10 mg/kg) antagonized very effectively the antinociceptive effects of xylazine in two tests: electrical stimulation of the rat's tail and the hot plate test in mice. 2-Diethylaminomethyl-1,4-benzodioxane (883 F), dibozane, ethomoxane, tolazoline and dibenamine were much less effective in rats. Azapetine, moxisylyte and phenoxybenzamine were as ineffective as propranolol, but Kö 1366, a potent β-adrenoceptor blocking agent was effective in high doses. Prindolol, another potent β-adrenoceptor blocking agent, only decreased the effect of xylazine on the startle. Atropine and mecamylamine did not change the effect of xylazine in rats. On the hot plate test in mice, dibozane, ethomoxane, tolazoline, phentolamine, dibenamine, chlorpromazine, clomipramine, pindolol, Kö 1366, atropine and atropine methyl nitrate were very effective in antagonizing the effect of xylazine, when both drugs were given intraperitoneally, but were less active when xylazine was given intracerebroventricularly. When the potential antagonist and xylazine were both administered into the cerebral ventricle of the brain, only piperoxan, yohimbine, tolazoline, clomipramine, Kö 1366, atropine and atropine methyl nitrate were effective. Phenoxybenzamine, azapetine, moxisylyte, propranolol and mecamylamine were ineffective by all routes of administration. These results suggest the involvement of receptors with properties in common with classical α-adrenoceptors in the antinociceptive action of xylazine, but these receptors seem to be distinct. In addition, in the hot plate test central cholinergic mechanisms could be involved as well as peripheral mechanisms.