The avermectins are a series 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring compounds are generated as fermentation products by Streptomyces avermitilis, a soil actinomycete. The avermectins block the transmittance of electrical activity in nerves and muscle cells by stimulating the release and binding of gamma-aminobutyric acid (GABA) at nerve endings. This causes an influx of chloride ions into the cells, leading to hyperpolarisation and subsequent paralysis of the neuromuscular systems. GABA-ergic receptors are found at the neuromuscular junctions and the central ventral cords in nematodes, whereas in mammals they are found primarily in the brain. Avermectin therapy is not without its drawbacks. Resistance to avermectins has been reported, which suggests use in moderation.
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