[Studies on the antinociceptive activity of guanabenz, with particular reference to clonidine and morphine (author's...

The antinociceptive activity of guanabenz, a new potent antihypertensive agent, and its interaction with alpha-adrenoceptors or opiate receptors, with particular reference to clonidine and morphine, were studied. Guanabenz, clonidine and morphine were found to possess a dose-dependent antinociceptive activity in mice and rats. In the tail flick assay, the antinociceptive activity of guanabenz and clonidine was antagonized by yohimbine but not by naloxone or phenoxybenzamine. Guanabenz, clonidine and morphine caused a concentration-dependent inhibition of the twitch response of transmurally stimulated guinea-pig ileum longitudinal muscle. Phentolamine and yohimbine reversed the twitch-inhibitory effects of guanabenz and clonidine, but naloxone failed to reverse this action. Guanabenz and low doses of clonidine caused locomotor hypoactivity. This action of both drugs was affected by yohimbine but not by phenoxybenzamine. In contrast, a high dose of clonidine caused locomotor hyperactivity which was affected by phenoxybenzamine but not by yohimbine. These results suggest that the antinociceptive activity of guanabenz, as in the case of clonidine, may be mediated by the activation of alpha 2-adrenoceptors and be independent from opiate receptors.