Bitonti A J, Sjoerdsma A, McCann P P, Kyle D E, Oduola A M, Rossan R N, Milhous W K, Davidson D E
Merrell Dow Research Institute, Cincinnati, OH 45215.
Science. 1988 Dec 2;242(4883):1301-3. doi: 10.1126/science.3057629.
Desipramine and several other tricyclic antidepressant drugs reverse chloroquine resistance in Plasmodium falciparum in vitro at concentrations observed in the plasma of human patients treated for depression. Reversal of resistance is associated with increased chloroquine accumulation in the parasite, probably because of inhibition of a putative chloroquine efflux pump. When owl monkeys (Aotus lemurinus lemurinus) infected with chloroquine-resistant Plasmodium falciparum were treated with chloroquine plus desipramine, their parasitemias were rapidly suppressed. Desipramine was found to be one of the most effective compounds yet described for the reversal of chloroquine resistance both in vitro and in vivo.
去甲丙咪嗪和其他几种三环类抗抑郁药在体外能逆转恶性疟原虫对氯喹的耐药性，其浓度与接受抑郁症治疗的人类患者血浆中观察到的浓度相同。耐药性的逆转与寄生虫中氯喹积累的增加有关，这可能是由于一种假定的氯喹外排泵受到抑制。当感染了对氯喹耐药的恶性疟原虫的夜猴（Aotus lemurinus lemurinus）用氯喹加去甲丙咪嗪治疗时，它们的疟原虫血症迅速得到抑制。去甲丙咪嗪被发现是迄今为止所描述的在体外和体内逆转氯喹耐药性最有效的化合物之一。
