The preparation and properties of (+)- and (--)-guanoxan.

Abstract

Abstract (±)-2-Aminomethyl-1, 4-benzodioxan has been resolved into its optically active isomers: (+)- and (-)-guanoxan have been synthesized from these. The pharmacological effects of racemic-guanoxan and of the two optical isomers have been compared on the isolated central ear artery of the rabbit, on the pithed rat in which pressor responses were evoked by stimulation of the thoraco-lumbar sympathetic outflow, and on the pre- and post-ganglionically stimulated nictitating membrane of the cat. The two isomers were equipotent in producing adrenergic neuron blockade. Initial catecholamine release was weak in the cat, but occurred more powerfully in the rabbit ear artery and in the rat. Ability to produce this effect resided mainly with the (+)-isomer. α-Adrenoreceptor blocking activity was detectable in the rat and was produced mainly by the (+)-isomer suggesting that its stereochemical configuration corresponds to that of D-(-)-noradrenaline. Ganglion blockade was an unimportant action of the compounds, but both isomers possessed weak atropine-like activity in the rat.