Meshnick Steven R
Department of Epidemiology, University of North Carolina, School of Public Health, Chapel Hill 27599-7435, USA.
Int J Parasitol. 2002 Dec 4;32(13):1655-60. doi: 10.1016/s0020-7519(02)00194-7.
Artemisinin and its derivatives are widely used throughout the world. The mechanism of action of these compounds appears to involve the heme-mediated decomposition of the endoperoxide bridge to produce carbon-centred free radicals. The involvement of heme explains why the drugs are selectively toxic to malaria parasites. The resulting carbon-centred free radicals are alkylate heme and proteins, one of which is the translationally controlled tumour protein. Clinically relevant artemisinin resistance has not been demonstrated, but it is likely to occur since artemisinin resistance has been obtained in laboratory models. At high doses, artemisinin can be neurotoxic but toxicity has not been found in clinical studies. The mechanism of neurotoxicity may be similar to the mechanism of action.
青蒿素及其衍生物在全世界广泛使用。这些化合物的作用机制似乎涉及血红素介导的内过氧化物桥分解，以产生碳中心自由基。血红素的参与解释了为何这些药物对疟原虫具有选择性毒性。产生的碳中心自由基会使血红素和蛋白质烷基化，其中一种蛋白质是翻译控制肿瘤蛋白。临床上尚未证实青蒿素耐药性，但由于在实验室模型中已获得青蒿素耐药性，因此很可能会出现。高剂量时，青蒿素可能具有神经毒性，但临床研究中未发现毒性。神经毒性机制可能与作用机制相似。
