Nelson N F, Saz H J
Exp Parasitol. 1983 Aug;56(1):55-69. doi: 10.1016/0014-4894(83)90096-6.
Amoscanate possesses chemotherapeutic activity against schistosomes, and in higher doses against many other helminths including filariids and Hymenolepis diminuta. The primary mode of action of this compound is unknown. Effects of the drug on the carbohydrate metabolism as well as on the tegumental and nephridial epithelia of H. diminuta were examined. At various time intervals after administration of the drug to rats infected with H. diminuta, the parasites were recovered and incubated in glucose-salts medium for 90 min. Chemotherapy resulted in decreases in succinate, lactate, and acetate recoveries, while ATP levels dropped. In addition, glycogen levels were depressed in drug-treated worms which were homogenized immediately upon isolation. Glycogen synthase I activity was inhibited 16-61% in cestodes obtained from Amoscanate-treated animals and homogenized immediately, but returned to normal levels after incubation for 90 min in glucose-salts medium prior to homogenization and assay. Phosphorylase a activity was found to be 25-30% higher in preparations of worms from drug-treated rats, which correlates with the rapid depletion of glycogen in parasites exposed to the drug. However, in contrast with glycogen synthase activity, the elevation of phosphorylase a activity in H. diminuta exposed to the drug was not readily reversible. Attempts to demonstrate activity of the drug in vitro by incubating intact cestodes directly with Amoscanate were unsuccessful. Thin sections of parasites obtained from Amoscanate-treated rats and examined by transmission electron microscopy revealed surface alterations of the tegument and nephridial canals. Alterations included bleb formation and erosion of microtriches from the tegument, as well as disappearance of microvilli from nephridial canals. However, these effects became manifest only after 4 or more hr exposure of the rat to the drug. Biochemical effects, on the other hand, were significant after 3 hr exposure.
硝硫氰胺对血吸虫具有化疗活性，高剂量时对包括丝虫和微小膜壳绦虫在内的许多其他蠕虫也有作用。该化合物的主要作用方式尚不清楚。研究了该药物对微小膜壳绦虫碳水化合物代谢以及对其体壁和肾管上皮的影响。给感染微小膜壳绦虫的大鼠给药后，在不同时间间隔收集寄生虫，并在葡萄糖盐培养基中孵育90分钟。化疗导致琥珀酸盐、乳酸盐和乙酸盐回收率降低，同时ATP水平下降。此外，药物处理后的蠕虫在分离后立即匀浆，其糖原水平降低。从经硝硫氰胺处理的动物获得并立即匀浆的绦虫中，糖原合酶I活性被抑制16 - 61%，但在匀浆和测定前在葡萄糖盐培养基中孵育90分钟后恢复到正常水平。发现来自药物处理大鼠的蠕虫制剂中磷酸化酶a活性高25 - 30%，这与暴露于药物的寄生虫中糖原快速消耗相关。然而，与糖原合酶活性相反，暴露于药物的微小膜壳绦虫中磷酸化酶a活性的升高不易逆转。直接将完整的绦虫与硝硫氰胺一起孵育以证明该药物体外活性的尝试未成功。从经硝硫氰胺处理的大鼠获得的寄生虫薄切片经透射电子显微镜检查显示体壁和肾管表面改变。改变包括体壁形成泡状突起和微毛侵蚀，以及肾管微绒毛消失。然而，这些影响仅在大鼠接触药物4小时或更长时间后才显现。另一方面，生化效应在接触药物3小时后就很明显。
