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 Ca 2+ channels. For example in guinea‐pig ileum, bisnordihydrotoxiferine ( p D' 2 3.92±0.09) and verapamil ( p D' 2 6.00±0.11) inhibited KCl induced contractions. Furthermore, bisnordihydrotoxiferine ( p D' 2 4.37±0.02) and verapamil ( p D' 2 6.83±0.10) also antagonized CaCl 2 induced contractions of K + ‐depolarized rat uterus. When compared with sodium nitroprusside, an antagonist of receptor operated Ca 2+ channels, bisnordihydrotoxiferine had no effect. However, in the aorta, the alkaloid (IC 50 , 6.10 × 10 −6 M) antagonized the intracellular calcium dependent transient contractions of noradrenaline and it was about four times more potent than procaine (IC 50 , 2.30 × 10 −5 M), a known inhibitor of the release of Ca 2+ 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.