A Pharmacological Study of Two Bisbenzylisoquinoline Alkaloids, Thalistyline and Obamegine

Publisher Website
Google Scholar
Abstract
Thalistyline, a monoquaternary bisbenzylisoquinoline alkaloid isolated from Thalictrum sp. inhibited respiration in anesthetized dogs. Thalistyline is about 1/4 as potent as d-tubocurarine in blocking neuromuscular transmission in the rat hemidiaphragm preparation. The pharmacological mechanism of action of the alkaloid is similar to that of d-tubocurarine. Obamegine did not exhibit curare-like activity. On the isolated rabbit aorta, contractions induced by an .alpha. adrenoreceptor agonist, phenylephrine, were antagonized by both alkaloids. Increasing concentrations of thalistyline produced parallel shifts to the right in the dose-response curves of phenylephrine. The pA2 [competitive antagonistic activity] value for the competitive pharmacological antagonism was 6.33. Obamegine also antagonized the effects of phenylephrine on the aorta, but at the higher concentration blockade did not appear to be competitive. Thalistyline and obamegine lowered blood pressure in normotensive dogs. The effect was transient. Repeated injections of the alkaloids resulted in tachyphylaxis to blood pressure lowering effects. Although alkaloids exhibited .alpha. adrenergic blockade in the vascular preparation, the mechanism for the hypotensive effect remains to be established.