Abstract: | The dimeric tertiary indole alkaloid bisnordihydrotoxiferine isolated from the root bark of Strychnos trinervis (Vell.) Mart. inhibited, on i.p. administration, Escherichia coli-induced diarrhoea and cholera toxin-stimulated intestinal fluid accumulation in mice. The respective ED50 values were 10.6 and 20.0 mg/kg. The activity of bisnordihydrotoxiferine was unaffected by nalorphine or yohimbine, suggesting that the opioid and α2-adrenoceptors respectively, are not important for its antidiarrhoeal action. In smooth muscle studies, bisnordihydrotoxiferine antagonized in a noncompetitive and reversible manner, the contractions produced by histamine, acetylcholine and substance P in guinea-pig ileum and by 5-hydroxytryptamine and arachidonic acid in rat fundic strip. The respective pD'2 values (mean ± SEM) were 5.21 ± 0.29, 5.20 ± 0.29, 5.35 ± 0.12, in the ileum and 4.95 ± 0.13 and 3.66 ± 0.12 in the fundic strip. The values of slopes of the regression lines differed significantly from unity in all cases. Bisnor was inactive against PGE2-induced contractions in the ileum. The mechanism of action of the alkaloid may be related to nonspecific antagonism of gastrointestinal smooth muscle stimulant activity of several endogenous substances. |