Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1692, USA.
Acta Trop. 2012 Jan;121(1):34-43. doi: 10.1016/j.actatropica.2011.10.007. Epub 2011 Oct 14.
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.
实验室和现场研究表明，伊维菌素是一种靶向无脊椎动物配体门控离子通道（LGIC）的药物，在标准药物给药后，其在人类血液中的浓度对疟蚊属蚊子具有很强的活性；因此，伊维菌素有望成为一种大规模的人类管理的内寄生虫药物，有助于抑制疟原虫传播。我们使用体外血液喂养试验评估了其他针对非洲疟疾传播媒介冈比亚按蚊的系统性 LGIC 靶向药物的活性。埃普里诺菌素、塞拉菌素、莫昔克丁和 N-叔丁基诺利斯波酰胺被评估为具有与伊维菌素相似作用模式的潜在系统性药物；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，吡虫啉和多杀菌素被评估为系统性药物，主要作为烟碱型乙酰胆碱受体通道的激动剂。只有埃普里诺菌素在与伊维菌素相当的浓度下杀死了冈比亚疟蚊。在亚致死剂量下，吡虫啉和莫昔克丁略微影响蚊子再次吸血的能力。大环内酯类药物，特别是埃普里诺菌素，导致被喂食血液的雌性蚊子明显失能和明显抑制恢复。这些数据是评估可能最终与伊维菌素联合使用或替代伊维菌素以控制未来疟原虫传播的药物的第一步。
