THE CHEMOTHERAPY OF RODENT MALARIA .36. CAUSAL PROPHYLAXIS .4. THE ACTIVITY OF A NEW 8-AMINOQUINOLINE, WR 225,448 AGAINST EXO-ERYTHROCYTIC SCHIZONTS OF PLASMODIUM-YOELII-YOELII
THE CHEMOTHERAPY OF RODENT MALARIA .36. CAUSAL PROPHYLAXIS .4. THE ACTIVITY OF A NEW 8-AMINOQUINOLINE, WR 225,448 AGAINST EXO-ERYTHROCYTIC SCHIZONTS OF PLASMODIUM-YOELII-YOELII
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DOI：
10.1080/00034983.1984.11811851
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发表时间：
1984-01-01
影响因子：
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通讯作者：
LANDAU, I
中科院分区：
文献类型：
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作者：
PETERS, W;ELLIS, D;LANDAU, I
光学显微镜和超微结构研究表明，WR 225，448（一种与伯氨喹有关的8-氨基喹啉）对幼大鼠肝脏中发育中的约氏疟原虫红细胞前EE小体造成严重损害。除了线粒体和核膜的损伤外，寄生虫中的分泌颗粒不能穿过寄生虫膜到达周围的宿主细胞质。WR 225，448的有效剂量远低于伯氨喹。在给药动物中也观察到肝损伤。这可能是实验性接种大量感染性蚊子唾液腺组织所产生的损伤的总和，这种损伤也见于未治疗的动物，加上药物本身的毒性作用。在化合物的临床前毒性试验中，必须特别注意这一方面。
Light microscope and ultrastructural studies show that WR 225,448, an 8-aminoquinoline related to primaquine, causes substantial damage to developing pre-erythrocytic EE schizonts of P. yoelii in the liver of young rats. In addition to lesions of the mitochondria and nuclear membranes, secretory granules in the parasite fail to reach the surrounding host cell cytoplasm across the parasite membrane. The effective dose of WR 225,448 is much lower than that of primaquine. Hepatic damage is also seen in treated animals. This may be the summation of domage produced by the experimental inoculation of a large quantity of infective salivary gland tissue from mosquitoes which is also seen in untreated animals plus toxic effects of the drug itself. Particular attention would have to be directed to this aspect in preclinical toxicity testing of the compound.