Relaxant properties of some aporphine alkaloids from Mahonia aquifolium.

In the present study we tested the effect of four aporphine alkaloids, corytuberine, magnoflorine, isothebaine and isocorydine, on the isolated rat aorta. Corytuberine and magnoflorine showed little effect as relaxants in KCl- and noradrenaline-induced contractions. They did not inhibit the phenylephrine concentration-response curve (CRC). Isothebaine and isocorydine showed relaxant properties in the rat aorta. They relaxed the contractions induced by noradrenaline to a greater extent than those induced by KCl and they also inhibited the noradrenaline-induced contraction in calcium-free solution. These alkaloids competitively shifted the phenylephrine CRC to the right and non-competitively the serotonin CRC. They seemed to inhibit both the influx of calcium into the cell, preferentially through receptor-regulated calcium channels, and the release of calcium from intracellular stores. Moreover, they appear to be antagonists of alpha 1-adrenoceptors. Study of structure-activity relationships of aporphine alkaloids in the inhibition of calcium influx via potential-operated Ca2+ channels yielded information indicative of the interaction of these substances with the benzothiazepine receptor.