Associate Certified Entomologist (ACE) Practice Exam

What is the MOA for macrocyclic lactones?

1. Block energy production

2. Disrupt the GABA-activated chloride channels

3. Inhibit cell replication

4. Interfere with calcium uptake

The correct answer is: Disrupt the GABA-activated chloride channels

The mode of action (MOA) for macrocyclic lactones, such as ivermectin and moxidectin, primarily involves disrupting the function of GABA-activated chloride channels. These compounds bind to glutamate-gated chloride channels and GABA (gamma-aminobutyric acid) receptors in the nervous systems of invertebrates, leading to the hyperpolarization of the nerve cells. This hyperpolarization results in paralysis and ultimately death of the parasite, making macrocyclic lactones effective antiparasitic agents. GABA is a critical neurotransmitter that inhibits neuronal excitability and regulates muscle function in both invertebrates and vertebrates, but macrocyclic lactones selectively target invertebrate channels. Due to the higher sensitivity of the parasites' nervous systems to these compounds compared to non-target organisms, macrocyclic lactones are considered safe for use in veterinary and some human medicine against parasitic infections. Other options are not relevant to the mechanism of action for macrocyclic lactones. For instance, blocking energy production, inhibiting cell replication, and interfering with calcium uptake pertain to different classes of drugs or mechanisms and do not apply to the well-established action of macrocyclic lactones.