BISNORDIHYDROTOXIFERINE AND VELLOSIMINE FROM STRYCHNOS-DIVARICANS ROOT - SPASMOLYTIC PROPERTIES OF BISNORDIHYDROTOXIFERINE

Bisnordihydrotoxiferine and vellosimine, two tertiary indole alkaloids have been isolated from the root of Strychnos divaricans. Bisnordihydrotoxiferine antagonized in a nonspecific manner, oxytocin and acetylcholine induced contractions in the rat uterus and acetylcholine and histamine responses in the guinea-pig ileum. Bisnordihydrotoxiferine, like verapamil, produced effects on voltage dependent Ca2+ channels. For example in guinea-pig ileum, bisnordihydrotoxiferine (pD2' 3.92+/-0.09) and verapamil (pD2' 6.00+/-0.11) inhibited KCl induced contractions. Furthermore, bisnordihydrotoxiferine (pD2' 4.37+/-0.02) and verapamil (pD2 6.83+/-0.10) also antagonized CaCl2 induced contractions of K+-depolarized rat uterus. When compared with sodium nitroprusside, an antagonist of receptor operated Ca2+ channels, bisnordihydrotoxiferine had no effect. However, in the aorta, the alkaloid (IC50, 6.10 X 10(-6) M) antagonized the intracellular calcium dependent transient contractions of noradrenaline and it was about four times more potent than procaine (IC50, 2.30 x 10(-5) m), a known inhibitor of the release of Ca2+ from intracellular stores. Bisnordihydrotoxiferine may produce nonspecific spasmolytic actions mainly by inhibiting intracellular calcium mobilization and to a lesser extent by inhibiting voltage dependent calcium channels in smooth muscles.