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.
D000700:Analgesics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D006993:Hypnotics and Sedatives; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013997:Time Factors
D000700:Analgesics; D006993:Hypnotics and Sedatives; D009281:Naphthalenes; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D013764:Tetrahydronaphthalenes; D003000:Clonidine