Explanation of atrial biphasic responses to isoxsuprine in the rabbit and guinea pig.

Isoxsuprine, a vasodilator agent, 2-(3 phenoxy-2 propylamino)-l-(p-hydroxyphenyl.) 1-propanol hydrochloride, was synthesized by Moed and Van Dijk in 1956 (1) and has a j3-stimulatory and adrenolytic action and a papaverine-like or a direct action as reported by Brucke et al. (2) and Ariens and Simonis (3). Lish et al. (4, 5) attributed a relaxing activity of the drug to the adrenergic fl-stimulatory action in some tissues and the direct action in other tissues when different kinds of non-vascular smooth muscle were used. However, Drinnon and Yelnosky (6) and Manley and Lawson (7) reported that the vaso dilator action of isoxsuprine was attributable mainly to the direct action of the drug. Preliminary observations showed atrial biphasic responses-initial stimulatory and then inhibitory responses-to a relatively high dose of isoxsuprine. This study was undertaken to investigate in details a mechanism of atrial biphasic responses to the drug in the rabbit and guinea pig.