Comparative evaluation of systemic drugs for their effects against Anopheles gambiae
Comparative evaluation of systemic drugs for their effects against Anopheles gambiae
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DOI：
10.1016/j.actatropica.2011.10.007
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发表时间：
2012-01-01
期刊：
影响因子：
2.7
通讯作者：
Foy, Brian D.
中科院分区：
文献类型：
--
作者：
Butters, Matthew P.;Kobylinski, Kevin C.;Foy, Brian D.
实验室和现场研究表明，伊维菌素，一种靶向无脊椎动物配体门控离子通道（LGIC）的药物，对按蚊属有强效活性。在标准药物施用后，伊维菌素可以使蚊子的血药浓度达到人血中的浓度;因此，伊维菌素有望成为一种大规模人类施用的杀寄生虫剂，可以帮助抑制疟疾寄生虫传播。我们评估了其他系统性LGIC靶向药物对非洲疟疾媒介冈比亚按蚊使用体外吸血试验的活动。埃普利诺菌素、赛拉菌素、莫昔克丁和N-叔丁基nodulisporamide被评价为与伊维菌素具有相似作用模式的潜在全身性药物;所有药物主要是无脊椎动物谷氨酸门控氯离子通道的激动剂。此外，烯啶虫胺和多杀菌素被评价为主要用作烟碱乙酰胆碱受体通道激动剂的全身药物。只有eprinomectin杀死了An。冈比亚，浓度与伊维菌素相当。在亚致死剂量下，烯啶虫胺和莫昔克丁轻微影响蚊子的再吸血能力。大环内酯（尤其是埃普利诺菌素）导致摄食血液的雌性动物的击倒显著增加，并显著抑制恢复。这些数据是评估药物的第一步，这些药物最终可能与伊维菌素结合使用，或取代伊维菌素，用于未来的疟疾寄生虫传播控制。(C)2011爱思唯尔有限公司版权所有。
Laboratory and field studies have shown that ivermectin, a drug that targets invertebrate ligand-gated ion channels (LGICs), is potently active against Anopheles spp. mosquitoes at concentrations present in human blood after standard drug administrations; thus ivermectin holds promise as a mass human-administered endectocide that could help suppress malaria parasite transmission. We evaluated other systemic LGIC-targeting drugs for their activities against the African malaria vector Anopheles gambiae using in vitro blood feeding assays. Eprinomectin, selamectin, moxidectin, and N-tert-butyl nodulisporamide were evaluated as potentially systemic drugs having similar modes of action to ivermectin; all primarily are agonists of invertebrate glutamate-gated chloride ion channels. Additionally, nitenpyram and spinosad were evaluated as systemic drugs that primarily work as agonists of nicotinic acetylcholine receptor channels. Only eprinomectin killed An. gambiae at concentrations that were comparable to ivermectin. At sub-lethal doses, nitenpyram and moxidectin marginally affected mosquito re-blood feeding ability. The macrocyclic lactones, particularly eprinomectin, caused significantly increased knockdown and significantly inhibited recovery in blood fed females. These data are a first step in evaluating drugs that might be eventually combined with, or substituted for ivermectin for future malaria parasite transmission control. (C) 2011 Elsevier B.V. All rights reserved.