Schmidt L H, Crosby R, Rasco J, Vaughan D
Antimicrob Agents Chemother. 1978 Nov;14(5):680-9. doi: 10.1128/AAC.14.5.680.
WR-184,806 and WR-226,253, two 4-quinolinemethanols structurally similar to WR-142,490 (mefloquine), have been studied in depth in owl monkeys infected with various drug-resistant and drug-susceptible strains of Plasmodium falciparum and P. vivax in an effort to provide support and guidance for projected evaluations in human volunteers. The results of these studies, confirmatory of preliminary appraisals, showed that WR-184,806 was approximately one-third as active as WR-142,490 against infections with a multidrug-resistant strain of P. falciparum, whereas WR-226,253 was twice as active. Additionally, the current studies showed: (i) that both WR-184,806 and WR-226,253 were significantly more active against infections with blood schizonts of P. vivax than against those of P. falciparum; (ii) that their activities against established infections with either Plasmodium species were functions of the total doses delivered, single doses being as effective as three or seven fractional doses given on successive days; (iii) that WR-184,806 could be administered intravenously as the phosphate salt and was curative via this route in single doses; and (iv) that based on comparative curative doses, WR-184,806 was slightly more active and WR-226,253 was seven times more active against infections with a multidrug-resistant strain of P. falciparum than was chloroquine against infections with a 4-aminoquinoline-susceptible strain.
WR-184,806和WR-226,253是两种4-喹啉甲醇，在结构上与WR-142,490（甲氟喹）相似。为了给计划在人类志愿者中进行的评估提供支持和指导，对感染了各种耐药和敏感恶性疟原虫及间日疟原虫菌株的夜猴进行了深入研究。这些研究结果证实了初步评估，表明WR-184,806对耐多药恶性疟原虫感染的活性约为WR-142,490的三分之一，而WR-226,253的活性则是其两倍。此外，目前的研究表明：（i）WR-184,806和WR-226,253对间日疟原虫血裂殖体感染的活性均显著高于对恶性疟原虫血裂殖体感染的活性；（ii）它们对两种疟原虫既定感染的活性是给药总剂量的函数，单次给药与连续三天给予的三个或七个分次剂量效果相同；（iii）WR-184,806可以以磷酸盐形式静脉给药，单次给药通过该途径可治愈；（iv）基于比较治愈剂量，WR-184,806对耐多药恶性疟原虫感染的活性略高于氯喹对4-氨基喹啉敏感菌株感染的活性，而WR-226,253的活性则是氯喹的七倍。
