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 (pD'₂ 3.92±0.09) and verapamil (pD'₂ 6.00±0.11) inhibited KCl induced contractions. Furthermore, bisnordihydrotoxiferine (pD'₂ 4.37±0.02) and verapamil (pD'₂ 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 × 10^?6M) antagonized the intracellular calcium dependent transient contractions of noradrenaline and it was about four times more potent than procaine (IC₅₀, 2.30 × 10^?5M), 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.