Coleman R E
Walter Reed Army Institute of Research, Washington, DC.
Am J Trop Med Hyg. 1990 Mar;42(3):196-205. doi: 10.4269/ajtmh.1990.42.196.
The influence of WR-238605 (8-[(4-amino-1-methyl-butyl) amino]-2,6-dimethoxy-4-methyl-5-[3-tri-fluoromethylphenoxyl] quinoline succinate) on the sporogonic development of a Plasmodium berghei ANKA clone was determined. Anopheles stephensi were fed on P. berghei infected mice treated 90 min earlier with 25 or 50 mg WR-238605/kg body weight. Mosquitoes engorging on drug-treated mice produced the same number of ookinetes as did those fed on controls; drug-fed mosquitoes produced fewer oocysts/mosquito than did controls. These oocytes developed more slowly than did those in control-fed mosquitoes. Sporozoites did not invade the salivary glands of drug-fed mosquitoes, nor did these mosquitoes transmit P. berghei to mice. Uptake of WR-238605 6 or 12 days after mosquitoes were infected with P. berghei had no effect on the percentage of mosquitoes with oocysts or the mean number of oocysts produced per mosquito. Oocyst development was significantly retarded in mosquitoes ingesting drug on day 6 postinfection. Subsequent salivary gland sporozoite infections were lighter in mosquitoes drug-fed on day 6 or day 12 than in control mosquitoes or mosquitoes drug-fed on day 18. These data indicate that WR-238605 has significant sporontocidal activity.
测定了WR-238605（8-[(4-氨基-1-甲基丁基)氨基]-2,6-二甲氧基-4-甲基-5-[3-三氟甲基苯氧基]喹啉琥珀酸盐）对伯氏疟原虫ANKA克隆子孢子发育的影响。将斯氏按蚊喂以90分钟前用25或50毫克WR-238605/千克体重处理过的感染伯氏疟原虫的小鼠。吸食经药物处理小鼠血液的蚊子产生的动合子数量与吸食对照小鼠血液的蚊子相同；吸食药物的蚊子每只产生的卵囊数量比对照蚊子少。这些卵囊的发育比吸食对照血液的蚊子中的卵囊更慢。子孢子没有侵入吸食药物的蚊子的唾液腺，这些蚊子也没有将伯氏疟原虫传播给小鼠。在蚊子感染伯氏疟原虫6天或12天后摄取WR-238605对有卵囊的蚊子百分比或每只蚊子产生的卵囊平均数没有影响。在感染后第6天摄取药物的蚊子中，卵囊发育明显受阻。在第6天或第12天吸食药物的蚊子中，随后的唾液腺子孢子感染比对照蚊子或在第18天吸食药物的蚊子轻。这些数据表明WR-238605具有显著的杀孢子体活性。
