avermectin

Avermectin refers to a group of macrocyclic lactone secondary metabolites produced by the soil bacterium Streptomyces avermitilis. The avermectin family includes several related compounds; the best known member is ivermectin, a derivative of avermectin B1 that is widely used in medicine. Avermectins are used as antiparasitic agents in veterinary medicine and, in refined forms such as ivermectin, in human medicine for infections caused by nematodes and ectoparasites.

Mechanism of action: They selectively bind to glutamate-gated chloride channels and, to a lesser extent, other receptor types in invertebrate nerve and muscle cells, increasing chloride conductance, causing hyperpolarization, paralysis, and death of the parasite. Mammals have fewer of these channels and possess drug efflux mechanisms (P-glycoprotein) that limit CNS exposure, contributing to a favorable safety profile at therapeutic doses; however, high doses or particular host genetic factors can allow CNS exposure and toxicity, particularly in certain dog breeds.

Applications: In veterinary medicine, avermectins are used to treat a wide range of helminth and ectoparasitic infections in cattle, horses, sheep, pigs, and companion animals; ivermectin is the most widely used member. In human medicine, ivermectin is used to treat onchocerciasis (river blindness), strongyloidiasis, and has roles in treatment regimens for other helminths and ectoparasitic infections such as scabies; it has also been used in mass drug administration programs in areas endemic for onchocerciasis and lymphatic filariasis. Resistance to avermectins has been reported in some parasite populations, prompting surveillance and combination therapy strategies.