Schmidt L H, Crosby R
Antimicrob Agents Chemother. 1978 Nov;14(5):672-9. doi: 10.1128/AAC.14.5.672.
Pilot appraisals of the activities of WR-194,965 and WR-204,165, two closely related o-cresol derivatives (both Mannich bases), in owl monkeys infected with the multidrug-resistant Vietnam Smith strain of Plasmodium falciparum showed that these compounds had similar levels of efficacy. Total course doses effecting 90% cures (CD(90)s) were 27 and 37 mg/kg of body weight for the respective compounds, values almost identical to the CD(90) of mefloquine (a highly promising 4-quinolinemethanol) against infections with the same strain, and the CD(90)s of chloroquine against infections with 4-aminoquinoline-susceptible strains. Expanded studies of the activities of WR-194,965 against infections with the Smith strain of P. falciparum and Vietnam Palo Alto strain of P. vivax, designed to guide projected evaluations in human volunteers, showed: (i) that the activity of this compound was a function of total dose administered, with single doses as effective as the same amount delivered in three or seven successive daily fractions; (ii) that all regimens effected rapid clearance of parasitemia; and (iii) that based on CD(90)s, this agent was twice as active against infections with the Palo Alto strain of P. vivax as against the Smith strain of P. falciparum. These findings, together with results of preclinical pharmacological studies pursued elsewhere, provided support for studies in human volunteers now underway.
对WR - 194,965和WR - 204,165这两种密切相关的邻甲酚衍生物（均为曼尼希碱）在感染多重耐药性越南史密斯株恶性疟原虫的夜猴体内的活性进行的初步评估表明，这些化合物具有相似的疗效水平。两种化合物实现90%治愈的总疗程剂量（CD(90)s）分别为27和37毫克/千克体重，这些数值几乎与甲氟喹（一种极具前景的4 - 喹啉甲醇）针对同一菌株感染的CD(90)以及氯喹针对4 - 氨基喹啉敏感菌株感染的CD(90)相同。针对WR - 194,965对恶性疟原虫史密斯株感染和间日疟原虫越南帕洛阿尔托株感染的活性开展的扩展研究，旨在为计划在人类志愿者中进行的评估提供指导，研究结果表明：（i）该化合物的活性是所给药总剂量的函数，单剂量与分三天或七天连续给药相同剂量的效果一样；（ii）所有给药方案均能使疟原虫血症迅速清除；（iii）基于CD(90)s，该药物对间日疟原虫帕洛阿尔托株感染的活性是对恶性疟原虫史密斯株感染活性的两倍。这些发现，连同其他地方进行的临床前药理学研究结果，为目前正在进行的人类志愿者研究提供了支持。
