milbemycin

Milbemycin is a group of macrocyclic lactone antiparasitic agents produced by Streptomyces species. The most widely used member is milbemycin oxime, a veterinary drug employed to prevent heartworm disease and to treat intestinal nematode infections. The milbemycin family includes related compounds, often marketed in oxime-bearing formulations for animal use.

Mechanism of action: Milbemycin binds to glutamate-gated chloride channels in invertebrate nerve and muscle cells. This increases chloride ion conductance, causing hyperpolarization, paralysis, and death of susceptible parasites. In mammals these channels are limited in the central nervous system, making the drug relatively safe when used as directed at approved doses.

Clinical use: In dogs and cats, milbemycin oxime is used alone or in fixed-dose combinations to prevent heartworm infection and to treat intestinal nematodes. Combinations with praziquantel target tapeworms, while other products pair milbemycin with lufenuron or spinosad for broader control. Common commercial formulations include Milbemax (milbemycin oxime + praziquantel), Sentinel (milbemycin oxime + lufenuron), and Trifexis (milbemycin oxime + spinosad).

Safety and resistance: Milbemycins can cause toxicity in certain dogs, particularly those with the MDR1 gene mutation, which can increase CNS exposure and lead to neurologic signs at higher doses. As with other macrocyclic lactones, resistance has been reported in some parasite populations, underscoring the need for responsible use and integrated parasite management.

Regulatory status: Milbemycin oxime is approved for veterinary use in many regions and is not generally approved for human therapy. Use should follow veterinary guidance regarding species, dosing, and potential drug interactions.