Antispasmodic activity of benzylisoquinoline alkaloids analogous to papaverine

Abstract

In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uterine muscular contractions induced by acetylcholine and calcium. The antagonism is more efficient for the alkaloid coclaurine which is even stronger than papaverine. The pA2 values obtained with each of the four alkaloids for both agents, acetylcholine and calcium, respectively, were as follows: reticuline (5.35 and 4.81), norarmepavine (5.55 and 4.09), coclaurine (7.42 and 6.91), papaverine (5.32 and 6.23). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the four alkaloids. The reduction is greater for the tonic phase, with the following IC50 values: reticuline 474 μM, norarmepavine 101 μM, coclaurine 68.9 μM, and papaverine 14.3 μM. The antispasmodic activity of the three alkaloids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, an intracellular effect, or both.