**4. Macrocyclic lactones (avermectins/milbemycins) and their mode of action**

Macrocyclic lactones have different commercialized products that show insecticidal activity against a broad range of parasitic nematodes and ectoparasites (ticks, mites, lice) that infest domestic animals [9, 10]. Avermectins that include doramectin, ivermectin, abamectin, and eprinomectin are the fermented products of actinomycete *Streptomyces avermitilis*. On the other hand, milbemectins including moxidectin and selamectin are the fermented products of *Streptomyces cyanogriseus*. On a chemical basis, avermectins differ based on the side chain of the lactone ring while milbemycins differ from each other because of the lactone skeleton [1].

The unequal larvicidal and adulticidal activity of IVM against Gastro-Intestinal Tract (GIT) roundworms and lungworms of ruminantia, porcine, and equine is its main factor of characterization [10, 11]. The control of microfilariae of canine heartworm *Dirofilaria immitis* is also achieved by the same chemical [1]. These chemicals do not have any anticestodal or antitrematodal activity nor are they ovicidal.

#### *Anthelmintic Drug Resistance in Livestock: Current Understanding and Future Trends DOI: http://dx.doi.org/10.5772/intechopen.104186*

Because of the nematicidal, acaricidal, and insecticidal activity of IVM, it is frequently used in sheep in different countries [4].

IVM along with other ML derivatives such as moxidectin is frequently used against haemonchosis in sheep due to its mode of action [1]. This increases their influence by binding to glutamate and GABA-gated chloride channel receptors in nematode and arthropod nerve cells. The whole process results in the opening of the channel and allows the entry of chloride ions (Cl− ). This will lead to the paralysis of the body wall, pharyngeal muscles, and uterine muscles in nematodes [12]. It is stated that the sensitivity of dissimilar chloride channel subunits to MLs and expression location are variable characters, and it can be accounted for the paralytic effect of different concentrations of MLs on the neuromuscular systems. It is also stated that nematode paralysis and body wall muscle paralysis can be proved serious for prompt exclusion, also pharyngeal muscle paralysis is more sensitive [13]. It has also been revealed that MLs cause the flaccid paralysis of the pharynx of nematodes along with moxidectin and IVM as it is more sensitive than somatic musculature, which shows that the target is the nervous system of parasites. If the concentration of MLs drops, then the motility of the parasites can be recuperated. As compared with somatic muscles, the paralysis of the pharyngeal muscles, as well as consequential inhibition of nourishing, can be longer. The reason for the ineffectiveness of ML derivatives against trematode and cestode parasites is that these worms do not have receptors at their glutamate-gated chloride channel.
