Abstract
The macrocyclic lactones (MLs) are one of the few classes of drug used in the control of the human filarial infections, onchocerciasis and lymphatic filariasis, and the only one used to prevent heartworm disease in dogs and cats. Despite their importance in preventing filarial diseases, the way in which the MLs work against these parasites is unclear. In vitro measurements of nematode motility have revealed a large discrepancy between the maximum plasma concentrations achieved after drug administration and the amounts required to paralyze worms. Recent evidence has shed new light on the likely functions of the ML target, glutamate-gated chloride channels, in filarial nematodes and supports the hypothesis that the rapid clearance of microfilariae that follows treatment involves the host immune system.
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Acknowledgments
We should look to thank Ray Kaplan, Balazs Rada and Andrew Moorhead for endless stimulating discussions and for all the help and reagents they and their groups have supplied. The parasites used in the authors’ laboratory were supplied by the NIH Filarial Research Resource Center. Research in the authors’ laboratory is supported by award R01AI103140 from the National Institutes of Health.
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Wolstenholme, A.J., Maclean, M.J., Coates, R. et al. How do the macrocyclic lactones kill filarial nematode larvae?. Invert Neurosci 16, 7 (2016). https://doi.org/10.1007/s10158-016-0190-7
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DOI: https://doi.org/10.1007/s10158-016-0190-7