Raether W, Fink E
Ann Trop Med Parasitol. 1979 Dec;73(6):505-26.
Floxacrine (HOE 991), 7-chloro-10-hydroxy-3-(4-trifluoromethylphenyl)3,4-dihydroacridine-1,9-(2H, 10H) dion, shows a high level of antimalarial action against blood-induced infection of drug-sensitive and drug-resistant lines of Plasmodium berghei in mice, rats and Syrian hamsters. The drug is also a potent blood schizontocide against drug-sensitive P. vinckei strains in rodents and P. cynomolgi in rhesus monkeys. The CD50/CD90 values against the drug-sensitive P. berghei strain ascertained in the '28-day test' in mice were 4.3/6.7 mg/kg after the oral route and 1.7/3.6 mg/kg after the subcutaneous (sc) route. In the 'two- and four-day test' the ED50 against sensitive P. vinckei was 0.7 mg/kg in both mice and rats. A moderate prophylactic effect could be demonstrated after the sc route probably due to a 'depot effect' of the water-insoluble active principle. Floxacrine was also highly active against P. berghei-lines which were resistant to chloroquine, mepacrine, dihydrofolate reductase inhibitors, sulfadoxine and dapsone. Resistance to HOE 991 could be developed in P. berghei and P. cynomolgi when the compound was used alone and administered repeatedly in subcurative doses. The antimalarial activity of the compound was not influenced by p-aminobenzoic acid or folic acid supplements in diets. Structural changes induced by floxacrine on pigment cytoplasm and nucleus in erythrocytic stages of P. berghei differed in some aspects from those of mepacrine and chloroquine. It is therefore assumed that the mode of action of floxacrine differs from that of the known antimalarial drugs. The general tolerance of the compound in rodents and rhesus monkeys is good and there is a wide range between the effective and maximum tolerated doses. Floxacrine was also effective at 100 ppm against pathogen Eimeria species in chickens, at 1000 mg/kg orally against Fasciola hepatica in rats and at 300-800 mg/kg orally against Heterakis spumosa in rats.
氟氯吖啶（HOE 991），即7-氯-10-羟基-3-（4-三氟甲基苯基）-3,4-二氢吖啶-1,9-（2H，10H）二酮，对小鼠、大鼠和叙利亚仓鼠体内伯氏疟原虫的药物敏感株和耐药株的血液感染表现出高度抗疟活性。该药物对啮齿动物体内的药物敏感型文氏疟原虫菌株以及恒河猴体内的食蟹猴疟原虫也是一种有效的血液裂殖体杀灭剂。在小鼠的“28天试验”中，针对药物敏感型伯氏疟原虫菌株测定的口服途径的CD50/CD90值为4.3/6.7 mg/kg，皮下（sc）途径为1.7/3.6 mg/kg。在“两天和四天试验”中，针对敏感型文氏疟原虫，小鼠和大鼠的ED50均为0.7 mg/kg。皮下给药后可能由于水不溶性活性成分的“贮库效应”，可显示出中等程度的预防效果。氟氯吖啶对氯喹、米帕林、二氢叶酸还原酶抑制剂、磺胺多辛和氨苯砜耐药的伯氏疟原虫株也具有高度活性。当单独使用该化合物并以亚治疗剂量反复给药时，伯氏疟原虫和食蟹猴疟原虫可能会对HOE 991产生耐药性。该化合物的抗疟活性不受饮食中对氨基苯甲酸或叶酸补充剂的影响。氟氯吖啶对伯氏疟原虫红细胞期色素细胞质和细胞核诱导的结构变化在某些方面与米帕林和氯喹不同。因此推测氟氯吖啶的作用方式与已知抗疟药物不同。该化合物在啮齿动物和恒河猴中的总体耐受性良好，有效剂量和最大耐受剂量之间的范围很宽。氟氯吖啶对鸡体内的病原体艾美耳属物种以百万分之100有效，对大鼠体内的肝片吸虫口服剂量为1000 mg/kg有效，对大鼠体内的泡翼线虫口服剂量为300 - 800 mg/kg有效。
