Sedative and analgesic actions of methoxylated 2-aminotetralins; involvement of alpha 1- and alpha 2-adrenoreceptors.

Three 5,8-dimethoxylated derivatives of 2-aminotetralin (2-AT) were compared with clonidine, methoxamine and phenylephrine in tests for sedation (inhibition of exploratory activity) and analgesia. In both tests the 2-AT derivatives were less potent than clonidine, but more potent than methoxamine or phenylephrine. Antagonism of the 2-AT derivative, DR-31, and clonidine by yohimbine in both tests argues for the involvement of alpha 2-adrenoreceptors in the mediation of these behavioral effects. alpha 1-Adrenoreceptors may also mediate an inhibition of exploratory activity since the inhibition induced by methoxamine was antagonized by phenoxybenzamine (POB) but not by yohimbine. The methoxylated 2-AT derivatives, which have previously been shown to exert potent peripheral alpha 1-agonism are now demonstrated to have sedative and analgesic effects characteristic of central alpha 2-adrenergic stimulation.