Harder A, Haberkorn A
Bayer AG, Institut für Parasitologie, Leverkusen, Federal Republic of Germany.
Parasitol Res. 1989;76(1):8-12. doi: 10.1007/BF00931064.
The anticoccidial properties of toltrazuril in Eimeria falciformis-infected mice were potentiated by the simultaneous application of pyrimethamine, trimethoprim, or sulfadimidine. The same drugs potentiate the effect of toltrazuril by killing E. tenella schizonts in chicken kidney-cell cultures. Activities of some enzymes of the respiratory chain, such as succinate-cytochrome C reductase and NADH oxidase and succinate oxidase from mouse liver, were reduced in the presence of toltrazuril. The same effects could be observed when the activities of NADH oxidase and fumarate reductase from the nematode Ascaris suum were determined in the presence of the drug. Vertebrate enzymes involved in pyrimidine synthesis, e.g., dihydrofolate reductase from chicken liver, were also affected by toltrazuril; however, this effect was 500 times weaker than that shown by pyrimethamine. Toltrazuril also showed an inhibitory effect on the dihydroorotate-cytochrome C reductase from mouse liver. Our results suggest that toltrazuril primarily affects the respiratory chain and secondarily, two enzymes involved in pyrimidine synthesis.
在感染了镰形艾美耳球虫的小鼠中，同时应用乙胺嘧啶、甲氧苄啶或磺胺二甲嘧啶可增强托曲珠利的抗球虫特性。同样这些药物通过在鸡肾细胞培养物中杀死柔嫩艾美耳球虫裂殖体来增强托曲珠利的效果。在存在托曲珠利的情况下，小鼠肝脏中一些呼吸链酶的活性，如琥珀酸 - 细胞色素C还原酶、NADH氧化酶和琥珀酸氧化酶，会降低。当在该药物存在的情况下测定来自猪蛔虫的NADH氧化酶和富马酸还原酶的活性时，也能观察到相同的效果。参与嘧啶合成的脊椎动物酶，例如来自鸡肝脏的二氢叶酸还原酶，也受到托曲珠利的影响；然而，这种影响比乙胺嘧啶所显示的弱500倍。托曲珠利还对小鼠肝脏中的二氢乳清酸 - 细胞色素C还原酶表现出抑制作用。我们的结果表明，托曲珠利主要影响呼吸链，其次影响参与嘧啶合成的两种酶。
