Raether W, Mehlhorn H
Zentralbl Bakteriol Mikrobiol Hyg A. 1984 Mar;256(3):335-41.
The floxacrine derivative S 82 5455, 7-chloro-1-( 4N - methylpiperazino -1N-imino)-10-hydroxy-1, 2, 3, 4-tetrahydro-3-(4-trifluoromethylphenyl)-9(10 H)- acridone , shows a high activity against blood induced infection of a drug-sensitive line of Plasmodium berghei in mice and rats. The dosis curativa minima/ dosis tolerata maxima values against the drug-sensitive P. berghei strain ascertained in the '28-day test' in mice, were 1.56 (X 5)/400 (X 1) mg/kg after the oral route 3.12(X 5)/400(X 1) mg/kg after the subcutaneous (sc) route. Morphological changes in erythrocytic stages of P. berghei following a single oral/sc dose of 25 and 50 mg/kg respectively in rats were at first swollen lacunes of the endoplasmic reticulum and extremely enlarged mitochondrion (6 h after treatment), then an apparent vacuolisation of the cytoplasm and pyknosis of the nucleus, as well as distinctly enlarged perinuclear space and later marked fissuring of the cytoplasm. After 23 h most of the parasites were destroyed by disruption of their pellicle. The majority of the degenerate parasites were situated outside of the apparently ruptured host cell. The remnants of damaged parasites and host cells disappeared completely from smears 96 h after treatment at all oral and sc doses used.
氟甲吖啶衍生物S 82 5455，即7-氯-1-（4N-甲基哌嗪-1N-亚氨基）-10-羟基-1,2,3,4-四氢-3-（4-三氟甲基苯基）-9（10H）-吖啶酮，对小鼠和大鼠体内伯氏疟原虫药物敏感株的血液感染显示出高活性。在小鼠的“28天试验”中确定的针对药物敏感的伯氏疟原虫菌株的最小治疗剂量/最大耐受剂量值，口服途径后为1.56（X 5）/400（X 1）mg/kg，皮下（sc）途径后为3.12（X 5）/400（X 1）mg/kg。在大鼠中分别单次口服/皮下注射25和50 mg/kg后，伯氏疟原虫红细胞阶段的形态变化起初是内质网出现肿胀的腔隙和线粒体极度增大（治疗后6小时），然后是细胞质明显空泡化和细胞核固缩，以及核周间隙明显增大，随后细胞质出现明显裂隙。23小时后，大多数寄生虫因表膜破裂而被破坏。大多数退化的寄生虫位于明显破裂的宿主细胞之外。在所有使用的口服和皮下剂量下，治疗96小时后，受损寄生虫和宿主细胞的残余物从涂片上完全消失。
