Isoxazolines: A Novel Chemotype Highly Effective on Ectoparasites

Efficient control of arthropod ectoparasite infestations has a long‐standing history in the agriculture and veterinary sectors, aiming to decrease the parasite burden of affected crops and animals. Ligand‐gated chloride channels (LGCCs) modulated by γ‐aminobutyric acid (GABA) and glutamate have been identified as suitable molecular targets, and several classes of potent parasiticides have been devised. Due to the increase in cross‐resistance and decreased development of new chemical entities, an urgent need for new parasiticides or prevention schemes has emerged. In the last decade, an innovative isoxazoline chemotype appears to offer promise for inhibiting LGCCs with a new mode of action and distinct binding site from that of historical agents. Considerable efforts have focused on optimizing the antiparasitic activity of isoxazolines and may provide the potential for future human use. Pest control: Isoxazolines belong to an intriguing compound class that has shown comprehensive ectoparasiticide activity toward ticks, fleas, and lice. Akin to the macrocyclic lactone avermectin, for which half the 2015 Nobel Prize in Physiology or Medicine was awarded, isoxazolines act on ligand‐gated chloride channels, but with a different mode of action, thereby breaking resistance. With the recent appearance of first‐market products in the veterinary field, an increased interest in the development of isoxazoline‐derived treatments is emerging, which may drive future use in the human health care sector.