Anisodus tanguticus (Max.) Pasch

Anisodamine , an alkaloid extracted from Anisodus tanguticus , is widely used in China in the treatment of septic shock, but its mechanism of action is unknown. We studied its antishock action in cats in a well controlled model of hemorrhagic shock. A bolus dose of 1 mg/kg was given intravenously 20 min after MABP was stabilized at 40-45 mm Hg, followed by i.v. infusion of 2 mg/kg/h during the oligemic period. Two hours post-reinfusion, MABP was significantly higher (106 +/- 10 mm Hg) in the drug-treated group than in shock cats receiving only vehicle (53 +/- 6 mm Hg, P less than 0.001). Anisodamine treated shock cats exhibited significantly lower cathepsin D activity (P less than 0.02) and amino-nitrogen concentration (P less than 0.001) than untreated shock animals. Plasma myocardial depressant factor (MDF) activity was significantly increased in the untreated shock cats (61 +/- 6 Units/ml), but the plasma accumulation of MDF was significantly blunted by anisodamine (32 +/- 5 Units/ml, P less than 0.01). Anisodamine did not increase superior mesenteric artery flow ( SMAF ) in this model of hemorrhagic shock as there was no significant difference in SMAF between the two shocked groups. Thus, the beneficial effect of anisodamine probably is not due to vasodilation of the splanchnic vasculature. In vitro analysis indicates that the drug has a direct anti-proteolytic action in cat pancreatic homogenates. This may partly explain the mechanism of its action, which appears to be complex.

The antishock effect of anisodamine (654-2) was observed in different kinds of experimental shock in groups of rabbits--due to late hemorrhage, superior mesenteric artery occlusion, and septic shock from peritonitis. The drug 654-2 significantly alleviated the progress of shock and increased the survival rate of the animals. The therapeutic effect of 654-2 was much better than that of other vasoactive drugs commonly used, such as norepinephrine, phenoxybenzamine, dopamine, and aramine. The antishock mechanism of 654-2 is probably partly due to its protective action on intestinal shock in preventing its effects becoming irreversible. The antishock action of 654-2 both by basic research workers and clinicians merits further study.

Hemorrhagic shock was experimentally produced in 123 rabbits which were divided into control groups and groups treated separately with anisodamine and norepinephrine. A comparison of their effect on the arterial blood pressure and mortality has shown that anisodamine has a much better therapeutic effect. However, without simultaneous and adequate volume replacement anisodamine appears to produce some harmful effects on rabbits in shock. It is suggested that the mechanism of its antishock effect lies in dilating the spastic arterioles present under shock conditions, and improving the microcirculation whereas norepinephrine on the contrary aggravates the microcirculatory disturbance through its vasoconstrictive action.