Macrocyclic
lactones, including
avermectins and
milbemycins, are novel
parasiticides and
insecticides that are produced through fermentation by soil-dwelling microorganisms. Although various macrocyclic
lactones may differ in their potency and safety, all of them are believed to share common pharmacologic/toxicologic mechanisms, i.e. leading to
paralysis and death of parasites and other target organisms via the activation of a
glutamate-gated chloride channel in the invertebrate nerve and muscle cells and/or through the effect on
gamma-aminobutyric acid (
GABA) receptors.
Ivermectin is the first macrocyclic
lactone that was released for use in both animals and humans, and has demonstrated both excellent efficacy and high tolerability in the treatment of parasite infestations. Other macrocyclic
lactones, such as
abamectin,
emamectin, and
moxidectin were subsequently commercialized and have been used as
insecticides and
acaricides for crop protection or
parasiticides for animal health. Although
ivermectin therapy is generally well tolerated, adverse effects that are usually transient and mild-to-moderate can occur. Severe adverse effects are rare and can generally be effectively controlled by symptomatic measures. Non-therapeutic exposures to
ivermectin and other macrocyclic
lactones may also result in toxic effects; significant toxicity however probably develops only after large amount of oral ingestion. Although the exact mechanisms remain unclear, macrocyclic
lactones in large doses may pass through the blood-brain barrier (BBB) to produce
GABA-mimetic toxic effects. Severely poisoned patients usually present with
coma,
hypotension,
respiratory failure, and even death. Despite the lack of specific
therapy, the prognosis is likely to be favorable unless the poisoned patients are complicated with severe
hypotension or
respiratory failure.