Lotilaner
[CAS# 1369852-71-0]

Identification

• Classification: Biochemical >> Inhibitor >> Neuronal signaling >> GABA receptor agonist
• Name: Lotilaner
• Synonyms: 3-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]-5-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]thiophene-2-carboxamide
• Molecular Formula: C₂₀H₁₄Cl₃F₆N₃O₃S
• Molecular Weight: 596.76
• CAS Registry Number: 1369852-71-0
• EC Number: 852-014-9
• SMILES: CC1=C(SC(=C1)C2=NO[C@@](C2)(C3=CC(=C(C(=C3)Cl)Cl)Cl)C(F)(F)F)C(=O)NCC(=O)NCC(F)(F)F

Properties

• Density: 1.7±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.593, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS09 Warning
• Hazard Statements: H400-H410
• Precautionary Statements: P273-P391-P501

Discovory and Applicatios

Lotilaner is an ectoparasiticide belonging to the isoxazoline class, developed for veterinary use in the treatment and prevention of ectoparasitic infestations in companion animals. It is primarily used to control fleas and ticks in dogs and cats by targeting the central nervous systems of these parasites. Lotilaner acts as a potent inhibitor of gamma-aminobutyric acid (GABA)-gated chloride channels in arthropods, resulting in uncontrolled neuronal stimulation, paralysis, and death of the parasites.

The development of lotilaner was part of a broader effort to create safer and more effective ectoparasiticides with rapid onset of action and sustained efficacy. Isoxazoline compounds were identified for their ability to selectively target insect and acarid GABA and glutamate-gated chloride channels, while sparing the mammalian equivalents. Lotilaner was developed by Elanco Animal Health (previously part of Novartis Animal Health and later acquired by Eli Lilly) as part of this new generation of antiparasitic agents.

Lotilaner was introduced commercially as an oral treatment under the trade name Credelio, with formulations designed specifically for dogs and cats. It received regulatory approval in several countries, including the United States, European Union, and Japan, for the treatment of flea (Ctenocephalides felis and Ctenocephalides canis) and tick (such as Rhipicephalus sanguineus, Ixodes ricinus, Ixodes scapularis, and Dermacentor variabilis) infestations. In clinical use, lotilaner begins killing fleas within four hours of administration and provides month-long protection with a single oral dose.

Lotilaner has a high degree of efficacy, rapid onset, and favorable safety profile, making it a preferred option for pet owners and veterinarians. Its palatable chewable tablet form aids in ease of administration. The pharmacokinetic profile of lotilaner includes good oral bioavailability, rapid absorption, and a half-life that supports monthly dosing. It is metabolized in the liver and excreted through both feces and urine.

In studies, lotilaner has demonstrated sustained activity against both adult fleas and newly emerging infestations, effectively breaking the flea life cycle. It also provides significant protection against tick species that act as vectors for various diseases, including Lyme disease and ehrlichiosis. This helps reduce the risk of pathogen transmission to both animals and humans, contributing to broader public health benefits.

Lotilaner is generally well tolerated in companion animals. Clinical trials and post-marketing data indicate a low incidence of adverse reactions, which may include gastrointestinal signs such as vomiting or diarrhea, and in rare cases, neurologic signs like ataxia or tremors. These effects are uncommon and typically resolve without treatment.

Beyond its use in dogs and cats, lotilaner has also been investigated for its potential application in the control of ectoparasites in other species, although its primary regulatory approvals remain limited to companion animals. It is not intended for use in livestock or humans.

In summary, lotilaner is an orally administered ectoparasiticide used in veterinary medicine to control flea and tick infestations in dogs and cats. It acts through selective inhibition of arthropod GABA-gated chloride channels, leading to rapid and effective parasite elimination. Its development represents a significant advancement in the field of veterinary parasitology, offering a combination of efficacy, safety, and convenience in parasite control.

References

2017. The novel isoxazoline ectoparasiticide lotilaner (Credelio�): a non-competitive antagonist specific to invertebrates ?-aminobutyric acid-gated chloride channels (GABACls). Parasites & Vectors, 10(1).
DOI: 10.1186/s13071-017-2470-4

2021. Collarette Elimination and Demodex Mite Eradication with Topical Lotilaner Ophthalmic Solution, 0.25%. Journal of Ocular Pharmacology and Therapeutics, 37(8).
DOI: 10.1089/jop.2021.0011

2024. Comparative speed of kill provided by lotilaner (Credelio�), sarolaner (Simparica Trio�), and afoxolaner (NexGard�) to control Amblyomma americanum infestations on dogs. Parasites & Vectors, 17(1).
DOI: 10.1186/s13071-024-06363-w