How do the macrocyclic lactones kill filarial nematode larvae?
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.
Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, 30602, USA. adrianw@uga.edu.|Department of Infectious Diseases, College of Veterinary Medicine, 501 D. W. Brooks Drive, Athens, GA, 30602, USA. adrianw@uga.edu.
Adrian J
AJ
Wolstenholme
Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, 30602, USA.
Mary J
MJ
Maclean
Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, 30602, USA.|Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK.
Ruby
R
Coates
Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, 30602, USA.|School of Biological Sciences, Medical Biology Centre, Queen's University, 97 Lisburn Road, Belfast, BT9 7BL, UK.
Ciaran J
CJ
McCoy
Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, 30602, USA.
Barbara J
BJ
Reaves
D000818:Animals; D005368:Filariasis / Q000188:drug therapy*; D005369:Filaricides / Q000494:pharmacology*; D005370:Filarioidea / Q000187:drug effects; D006801:Humans; D047029:Lactams, Macrocyclic; D007814:Larva / Q000187:drug effects*; D009854:Onchocerca / Q000187:drug effects
D005369:Filaricides; D047029:Lactams, Macrocyclic
Glutamate-gated chloride channel; Heartworm; Ivermectin; Lymphatic filariasis; Moxidectin; Onchocerciasis