Sedative effects of α-sympathomimetic drugs and their antagonism by adrenergic and cholinergic blocking drugs

The depressing action of a number of α-sympathomimetic agents on the central nervous system was studied in chickens and mice. Clonidine, 2-(2,6-dimethylphenylamino)-2- Δ 2-oxazolidine 1–3, tetryzoline, naphazoline, tramazoline xylazine and oxymetazoline induced a loss of the righting reflex in chickens and prolonged the sleeping time induced by chloral in mice. These effects were dose-dependent and much more potent for the two former drugs. The actions in chickens and mouse were antagonized by previous treatment with four α-adrenergic blocking drugs (tolazoline, phentolamine, piperoxane, dibenamine) but not phenoxybenzamine. In chickens, chlorpromazine and imipramine also antagonized the action, but haloperidol was an antagonist only for naphazoline and tetryzoline. In mice, but not in chickens, atropine and mecamylamine were strong antagonists. These results suggest that activation of α-adrenergic receptors in the brain induces sedation and the involvement of cholinergic pathways in mice for this effect.