In mice given a high-fat diet, (S)-(-)-Levamisole (Levamisole) (50 μg/ml and 200 μg/ml; oral; 30 days) inhibits weight gain [2].

Absorption, Distribution and Excretion
Levamisole is rapidly absorbed in the gastrointestinal tract (2 hours). Metabolism/Metabolites Primarily metabolized in the liver (extensively), producing active and inactive metabolites. Biological Half-Life 4.4–5.6 hours (biphasic)

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
Levamisole has been discontinued for human use in the United States due to its potential to cause agranulocytosis, but it is still used as an anthelmintic in other countries. There is currently no publicly available information regarding its excretion in breast milk. Some information suggests that levamisole use may be acceptable for breastfeeding women. However, due to limited experience with levamisole use during lactation, alternative medications may be preferred, especially when breastfeeding newborns or premature infants. The World Health Organization recommends that pregnant women taking levamisole should not breastfeed.
◉ Effects on Breastfed Infants
In the Democratic Republic of Congo, a cohort study of 33 infants followed hospitalized mothers taking nifurolimus who breastfed (the extent of breastfeeding was not specified). Thirty mothers received a complete course of 30 oral nifurulimus doses (15 mg/kg daily) and 14 intravenous doses of efornithine (400 mg/kg daily) for 7 days to treat human trypanosomiasis (sleeping sickness). Six of the breastfeeding mothers also received levamisole. No serious adverse events were reported in any of the breastfed infants.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Protein binding
20-25%

[1]. Lewis JA, et al. Levamisole: A Positive Allosteric Modulator for the α3β4 Nicotinic Acetylcholine Receptors Prevents Weight Gain in the CD-1 Mice on a High Fat Diet. Curr Pharm Des. 2017;23(12):1869-1872.
[2]. Mehta KP, et al. Immunoregulatory treatment for minimal change nephrotic syndrome. Arch Dis Child. 1986;61(2):153-158.

Levamisole is a 6-phenyl-2,3,5,6-tetrahydroimidazole[2,1-b][1,3]thiazole with an S configuration. It (usually in hydrochloride form) is used to treat parasitic infections in pigs, sheep, and cattle, and was previously used in humans as adjunctive therapy for various cancers. It is also widely used as a dopant for cocaine. It has anti-nematode, antirheumatic, immunomodulatory, immunoadjuvant, and EC 3.1.3.1 (alkaline phosphatase) inhibitor effects. It is the enantiomer of dextromisole. Levamisole is an anthelmintic that has been widely used to treat parasitic, viral, and bacterial infections. Manufactured by Janssen Pharmaceuticals, levamisole was initially used in 1969 for the treatment of helminth infections. In 1990, the U.S. Food and Drug Administration (FDA) approved levamisole as adjunctive therapy for colon cancer. Prior to this, levamisole was used as an antirheumatic therapy for patients with rheumatoid arthritis in the 1970s and 1980s. Due to its immunomodulatory effects, the drug has been investigated for the treatment of various immune-mediated diseases, with some studies showing positive results. It has also been used in combination with other drugs to treat various cancers. Because levamisole could cause serious adverse reactions, including agranulocytosis, it was withdrawn from the US market in 2000. Notably, levamisole has been found to be adulterated with cocaine, potentially causing various adverse reactions in users. Levamisole is an anthelmintic. Levamisole, in combination with fluorouracil, was used to treat Dukes stage C colon cancer, restoring immune function by stimulating antibody production, enhancing T cell activity, and enhancing macrophage function. (NCI04) Levamisole is an anthelmintic that has been experimentally used to treat rheumatic diseases, demonstrating its ability to restore immune responses by enhancing macrophage chemotaxis and T lymphocyte function. However, this immune-enhancing effect appears to be beneficial for rheumatoid arthritis, but side effects have been reported, including dermatitis, leukopenia, thrombocytopenia, and nausea and vomiting. (Quoted from Smith and Reynard, Textbook of Pharmacology, 1991, pp. 435-436)
See also: levamisole hydrochloride (salt form); levamisole phosphate (salt form); doramectin; levamisole (component).
Indications

Used as adjuvant therapy after surgical resection in patients with Dukes C stage colon cancer, in combination with fluorouracil. Also used to treat malignant melanoma and head and neck cancer.
Mechanism of Action

The mechanism of action of levamisole as an antiparasitic drug appears to be related to its agonistic effect on L-type nicotinic acetylcholine receptors in the muscle of nematodes. This agonistic effect reduces the ability of male nematodes to control their reproductive muscles, thereby limiting their mating ability. The mechanism of action of levamisole as an anticancer drug in combination with fluorouracil is not fully understood. The effects of levamisole on the immune system are complex. The drug appears to restore impaired immune function rather than stimulating an immune response to above-normal levels. Levamisole can stimulate antibody formation against multiple antigens, enhance T cell responses by stimulating T cell activation and proliferation, enhance the function of monocytes and macrophages (including phagocytosis and chemotaxis), and increase neutrophil migration, adhesion, and chemotaxis.

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Pharmacodynamics
Levamisole is a synthetic imidazothiazole derivative widely used to treat worm infections in humans and animals. As an anthelmintic, it may act by targeting nicotinic acetylcholine receptors in nematodes. As an immunomodulator, levamisole appears to be an immunostimulant; studies have shown that in stage III colon cancer patients receiving adjuvant levamisole in combination with 5-fluorouracil (5-FU), levamisole can increase the number of NK cells and activated T cells.

C11H12N2S

204.2914

204.072

14769-73-4

Levamisole hydrochloride;16595-80-5;Tetramisole hydrochloride;5086-74-8;Dexamisole;14769-74-5

26879

White to off-white solid powder

1.3±0.1 g/cm3

344.4±45.0 °C at 760 mmHg

230 - 233ºC

162.1±28.7 °C

0.0±0.8 mmHg at 25°C

1.713

1.85

0

2

1

14

246

1

S1C([H])([H])C([H])([H])N2C1=N[C@@]([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C2([H])[H]

HLFSDGLLUJUHTE-SNVBAGLBSA-N

InChI=1S/C11H12N2S/c1-2-4-9(5-3-1)10-8-13-6-7-14-11(13)12-10/h1-5,10H,6-8H2/t10-/m1/s1

(6S)-6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole

LevamisoleErgamisolDecarisLevotetramisoleSolaskilKetrax

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 (~489.50 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.24 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 (12.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 (12.24 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.)