Antagonism by tricyclic antidepressants of reserpine-induced hypothermia in mice. Involvement of postsynaptic alpha 2-adrenoceptors.

The effects of adrenoceptor blocking agents and cyproheptadine on the antagonism by the antidepressants imipramine, desipramine and maprotiline, of reserpine-induced hypothermia in mice were studied. The anti-reserpine effect of the antidepressants was reduced by phenoxybenzamine, prazosin, yohimbine and d,1-propranolol, the two latter drugs exhibiting the strongest effect. Practolol was ineffective, while cyproheptadine potentiated the effect of maprotiline and was inactive towards imipramine and desipramine. Furthermore, the anti-reserpine effect of desipramine (the other antidepressants not being studied) was also reduced by piperoxan and l-propranolol, but not by d-propranolol. The reserpine-induced hypothermia was antagonized by clonidine and this effect was completely blocked by yohimbine and partly reduced by prazosin. These results confirm that the antagonism by tricyclic antidepressants of reserpine-induced hypothermia depends on the activation of noradrenergic mechanisms and indicate that this effect is mediated not only by alpha 1- and beta-, but also by postsynaptic alpha 2-adrenoceptors.