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Comparative evaluation of systemic drugs for their effects against Anopheles gambiae.

Abstract
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.
AuthorsMatthew P Butters, Kevin C Kobylinski, Kelsey M Deus, Ines Marques da Silva, Meg Gray, Massamba Sylla, Brian D Foy
JournalActa tropica (Acta Trop) Vol. 121 Issue 1 Pg. 34-43 (Jan 2012) ISSN: 1873-6254 [Electronic] Netherlands
PMID22019935 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Insecticides
  • Membrane Transport Modulators
Topics
  • Animals
  • Anopheles (drug effects)
  • Female
  • Insecticides (pharmacology)
  • Membrane Transport Modulators (pharmacology)
  • Survival Analysis

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