What is the mechanism of Lotilaner?

Lotilaner is a potent ectoparasiticide belonging to the isoxazoline class of compounds. It is widely used in veterinary medicine, particularly for the treatment and prevention of ectoparasitic infestations in companion animals such as dogs and cats. Understanding the mechanism of action of Lotilaner is crucial for appreciating how this drug effectively eliminates and controls parasitic infestations.

The primary mechanism of action of Lotilaner involves its ability to interfere with the normal functioning of the nervous system of arthropod parasites such as fleas and ticks. Lotilaner exerts its parasiticidal effects by targeting and inhibiting specific ligand-gated chloride channels, particularly the gamma-aminobutyric acid (GABA)-gated chloride channels and glutamate-gated chloride channels.

GABA is a major inhibitory neurotransmitter in the nervous system of arthropods. Under normal physiological conditions, GABA binds to its receptors on the chloride channels, leading to the opening of these channels and subsequent influx of chloride ions into the neuron. This influx of chloride ions hyperpolarizes the neuronal membrane, making it less likely for the neuron to fire and thereby exerting an inhibitory effect on neurotransmission. By inhibiting GABA-gated chloride channels, Lotilaner prevents the influx of chloride ions, leading to sustained neuronal excitation. This results in hyperexcitation, paralysis, and ultimately the death of the parasite.

Similarly, Lotilaner affects glutamate-gated chloride channels, which play a role in the regulation of neuromuscular transmission in arthropods. Glutamate typically activates these channels, causing an influx of chloride ions that inhibits muscle contraction. By blocking these channels, Lotilaner induces uncontrolled muscular contraction, leading to paralysis of the parasite.

One of the notable advantages of Lotilaner is its selectivity. It selectively targets the GABA-gated and glutamate-gated chloride channels of arthropods without significantly affecting similar channels in the host animal. This selectivity is crucial for the safety and effectiveness of the drug, as it minimizes the risk of adverse effects in the treated animals.

Pharmacokinetically, Lotilaner is characterized by its rapid absorption and prolonged duration of action. After oral administration, the drug is quickly absorbed into the bloodstream and distributed throughout the body. It reaches its peak plasma concentration within a few hours, ensuring a swift onset of action. Furthermore, Lotilaner has a long half-life, allowing it to provide extended protection against parasitic infestations with a single dose.

Lotilaner’s high efficacy, combined with its favorable pharmacokinetic profile, makes it an attractive option for the treatment and prevention of flea and tick infestations in companion animals. It has been demonstrated to be highly effective in killing multiple species of fleas and ticks, including those resistant to other classes of parasiticides. Additionally, Lotilaner is available in various formulations, including oral chewable tablets, which enhance ease of administration and compliance in pet owners.

In conclusion, Lotilaner is a highly effective ectoparasiticide that works by inhibiting GABA-gated and glutamate-gated chloride channels in arthropod parasites. Its mechanism of action results in hyperexcitation, paralysis, and death of the parasites. The selectivity of Lotilaner for parasite-specific channels, along with its rapid absorption and prolonged duration of action, contributes to its efficacy and safety in treating and preventing flea and tick infestations in companion animals.