Selamectin targets glutamate-gated chloride channels in neurons and pharyngeal muscles of invertebrates. By activating these channels, it causes hyperpolarization of the neuronal membrane, leading to paralysis and/or death of the parasite. It also enhances GABA-gated chloride channel opening in nematodes. Additionally, it is a P-glycoprotein substrate and inhibitor, with an IC50 of 120 nM.

Radiolabeled selamectin was found to be a P-glycoprotein (P-gp) substrate with a secretion/absorption ratio of 4.7 when it was transported across the Caco-2 monolayer. In peripheral blood lymphocytes (PBL), selamectin inhibits Rh-123 efflux at a dose that is comparable to verapamil's inhibitory effect [2].
In vitro, Selamectin demonstrates potent antiparasitic activity. In an H. contortus larval development assay, Selamectin (0.1 μg/ml) shows growth inhibition. It is more potent than ivermectin and moxidectin against certain pathogens, with an MIC of 2-4 μg/mL vs. M. ulcerans, showing 8-fold greater potency. It inhibits rubidium efflux and activates chloride channels, leading to parasite paralysis.

B can be successfully avoided with topical selamectin 6 mg/kg once every two months. infection in cats with malayi. Twice a year, topical selamectin can stop microfilariae from circulating [1].
In vivo, Selamectin is highly effective as a topical treatment for companion animals. A single topical dose (6-12 mg/kg) achieves 100% mite reduction in sarcoptic mange, compared to 26% with oral ivermectin. It provides >90% flea control at 30 days and up to 99.8% at 90 days. Its broad-spectrum activity covers heartworms, fleas, ear mites, sarcoptic mange, ticks, and various intestinal worms.

In vitro receptor/enzyme assays for Selamectin are not standard, as its primary targets are ion channels in parasites. Its activity is assessed in functional assays using parasite preparations, such as the H. contortus larval development assay, where the compound's ability to inhibit larval growth is measured. Its effect on glutamate-gated chloride channels can be studied using electrophysiology on isolated neurons or by measuring ion flux in membrane preparations.

In vitro cellular assays for Selamectin are not typically performed on mammalian cells, as its primary activity is against parasites. However, its interaction with P-glycoprotein can be studied in cell lines overexpressing this transporter, measuring the compound's ability to inhibit the efflux of a fluorescent P-gp substrate. Its cytotoxic effects on parasite cells are assessed in culture.

In vivo animal experiments for Selamectin are conducted in dogs and cats, the target species for this parasiticide. Efficacy studies involve administering the compound topically (spot-on formulation) and then challenging the animals with parasites such as fleas, ticks, or heartworm larvae. Efficacy is measured by counting surviving parasites or by assessing the prevention of infection.

Selamectin is administered topically for its primary indication. As a topical agent, systemic absorption is minimal, and the drug acts locally at the site of application and systemically through absorption. It is a P-glycoprotein substrate, which may affect its distribution and excretion. Its PK profile in dogs and cats has been characterized, showing a long half-life and sustained efficacy.

Selamectin has a well-established safety profile in companion animals. It is generally well-tolerated, with a low incidence of adverse effects. Its safety in MDR1-mutant canine models is notable, as it has 5-10× lower brain accumulation compared to ivermectin in P-gp-deficient models, reducing the risk of neurotoxicity.

[1]. First study of topical selamectin efficacy for treating cats naturally infected with Brugia malayi and Brugia pahangi under field conditions. Parasitol Res. 2019 Apr;118(4):1289-1297.

[2]. Selamectin is a potent substrate and inhibitor of human and canine P-glycoprotein. J Vet Pharmacol Ther. 2005 Jun;28(3):257-65.

Selamectin is a milbemycin class of drugs. Selamectin is a topical anthelmintic used to treat and prevent heartworm, flea, ear mite, scabies, and certain tick infections in dogs and cats, and to prevent heartworm, flea, ear mite, hookworm, and roundworm infections in cats. It can also eliminate two lungworms in cats and one in dogs. This drug is distributed by Zoetis, a former subsidiary of Pfizer. Its structure is related to ivermectin and milbemycin. Selamectin is not approved for human use. See also: Salorana; Selamectin (ingredients). Indications: Cats and dogs: For the treatment and prevention of flea infestations caused by the genus Ctenocephalides after a single dose, with effects lasting one month. This is due to the product's adult, larval, and ovicidal properties. The product retains its ovicidal effect for up to 3 weeks after administration. By reducing flea populations, monthly treatment of pregnant and lactating animals also helps prevent flea infestation in puppies before 7 weeks of age. This product can be used as part of a flea allergy dermatitis treatment regimen; its ovicidal and larval-killing effects help control existing environmental flea infestations in areas accessible to the animal. Monthly administration can prevent canine heartworm disease caused by Dirofilaria immitis. This product is safe for use in animals already infected with adult worms; however, according to good veterinary practice, it is recommended that all animals aged 6 months and older living in countries with vectors be tested for adult Dirofilaria immitis infection before starting this product. Even with monthly use of this product, regular testing for adult Dirofilaria immitis infection in dogs is recommended as an important part of a heartworm prevention strategy. This product is ineffective against adult Dirofilaria immitis. Used to treat ear mites (Otodectes cynotis). Cats: Used to treat cat fleas (Felicola subrostratus), adult roundworms (Toxocara cati), adult hookworms (Ancylostoma tubaeforme), cat fleas (Trichodectes canis), and scabies (caused by Sarcoptes scabiei). A single dose can treat and prevent flea infestations caused by Ctenocephalides spp., with effects lasting up to one month. This is due to the product's adult, larval, and ovicidal properties. The product retains its ovicidal effect for up to three weeks after administration. Monthly treatment of pregnant and lactating animals by reducing flea populations also helps prevent flea infestations in pups before seven weeks of age. This product can be used as part of a flea allergy dermatitis treatment regimen; its ovicidal and larval-killing effects help control existing environmental flea infestations in the animal's living area. Monthly administration can prevent canine heartworm disease caused by Dirofilaria immitis. This product is safe for use in animals already infected with adult canine heartworms. However, according to good veterinary practice, it is recommended that all animals aged 6 months and older living in countries with vectors be tested for adult canine heartworm infection before starting this product. Even with monthly administration, regular testing for adult canine heartworm infection in dogs is recommended as an important part of a canine heartworm prevention strategy. This product is ineffective against adult canine heartworms. It is used to treat ear mites (Otodectes cynotis). Cats: Treatment of feline fleas (Felicola subrostratus); treatment of adult feline toxocara cati; treatment of adult canine hookworm (Ancylostoma tubaeforme). Dogs: Treatment of canine fleas (Trichodectes canis); treatment of scabies (caused by Sarcoptes scabiei); treatment of adult canine toxocara canis.
Cats and Dogs: A single dose can treat and prevent flea infestations caused by Ctenocephalides spp., with effects lasting up to one month. This is due to the product's adult, larval, and ovicidal properties. Ovicidal activity persists for up to 3 weeks after administration. Monthly treatment of pregnant and lactating animals by reducing flea populations also helps prevent flea infestations in pups before 7 weeks of age. This product can be used as part of a flea allergy dermatitis treatment regimen; its ovicidal and larval-killing effects help control existing environmental flea infestations in areas accessible to the animal. Monthly administration can prevent canine heartworm disease caused by Dirofilaria immitis. Stronghold is safe for use in animals already infected with adult Dirofilaria immitis; however, according to good veterinary practice, it is recommended that all animals aged 6 months and older living in countries with vectors be tested for adult Dirofilaria immitis infection before initiating treatment with Stronghold. Even with monthly Stronghold administration, regular testing for adult canine heartworm infection in dogs is recommended as an important part of a canine heartworm prevention strategy. This product is ineffective against adult canine heartworm. It is used to treat ear mites (Otodectes cynotis). Cats: Treats feline flea (Felicola subrostratus) infection; treats adult feline toxocara cati infection; treats adult canine hookworm (Ancylostoma tubaeforme) infection. Dogs: Treats canine flea (Trichodectes canis) infection; treats sarcoptes scabies (caused by Sarcoptes scabiei); treats adult canine toxocara canis infection.
Selamectin is marketed under the brand names Revolution and Stronghold. It is a second-generation, semi-synthetic avermectin. It is a monosaccharide avermectin with a unique structural profile. It is used worldwide as a broad-spectrum parasiticide for dogs and cats.

C43H63NO11

769.96000

769.44

220119-17-5

220119-17-5

9578507

White to off-white solid powder

1.4±0.1 g/cm3

917.0±65.0 °C at 760 mmHg

508.4±34.3 °C

0.0±0.6 mmHg at 25°C

1.618

6.83

3

12

4

55

1550

14

C[C@H]1CC[C@]2(C[C@@H]3C[C@H](O2)C/C=C(/[C@H]([C@H](/C=C/C=C/4\CO[C@H]\5[C@@]4([C@@H](C=C(/C5=N/O)C)C(=O)O3)O)C)O[C@H]6C[C@@H]([C@H]([C@@H](O6)C)O)OC)\C)O[C@@H]1C7CCCCC7

AFJYYKSVHJGXSN-XHKIUTQPSA-N

InChI=1S/C43H63NO11/c1-24-11-10-14-30-23-50-40-36(44-48)27(4)19-33(43(30,40)47)41(46)52-32-20-31(16-15-25(2)38(24)53-35-21-34(49-6)37(45)28(5)51-35)54-42(22-32)18-17-26(3)39(55-42)29-12-8-7-9-13-29/h10-11,14-15,19,24,26,28-29,31-35,37-40,45,47-48H,7-9,12-13,16-18,20-23H2,1-6H3/b11-10+,25-15+,30-14+,44-36-/t24-,26-,28-,31+,32-,33-,34-,35-,37-,38-,39-,40+,42+,43+/m0/s1

(1R,4S,5'S,6R,6'S,8R,10E,12S,13S,14E,16E,20R,21Z,24S)-6'-cyclohexyl-24-hydroxy-21-hydroxyimino-12-[(2R,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~129.88 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (3.25 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (3.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)