Su J, Hock C E, Lefer A M
Naunyn Schmiedebergs Arch Pharmacol. 1984 Apr;325(4):360-5. doi: 10.1007/BF00504382.
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.
山莨菪碱是从唐古特山莨菪中提取的一种生物碱,在中国广泛用于治疗感染性休克,但其作用机制尚不清楚。我们在一个控制良好的失血性休克猫模型中研究了其抗休克作用。在平均动脉血压(MABP)稳定在40 - 45 mmHg后20分钟,静脉注射1 mg/kg的大剂量药物,随后在少尿期以2 mg/kg/h的速度静脉输注。再灌注两小时后,药物治疗组的MABP显著高于仅接受赋形剂的休克猫(106±10 mmHg比53±6 mmHg,P<0.001)。与未治疗的休克动物相比,山莨菪碱治疗的休克猫组织蛋白酶D活性(P<0.02)和氨基氮浓度(P<0.001)显著降低。未治疗的休克猫血浆心肌抑制因子(MDF)活性显著增加(61±6单位/ml),但山莨菪碱显著抑制了MDF的血浆蓄积(32±5单位/ml,P<0.01)。在这个失血性休克模型中,山莨菪碱并没有增加肠系膜上动脉血流量(SMAF),因为两个休克组之间的SMAF没有显著差异。因此,山莨菪碱的有益作用可能不是由于内脏血管舒张。体外分析表明,该药物在猫胰腺匀浆中具有直接的抗蛋白水解作用。这可能部分解释了其作用机制,其作用机制似乎很复杂。