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 (2 hours) from the gastrointestinal tract.

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Metabolism / Metabolites
Primarily hepatic (extensive) with both active and inactive metabolites.

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Biological Half-Life
4.4-5.6 hours (biphasic)

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Levamisole is no longer marketed for human use in the United States because can cause agranulocytosis, but it is used as an anthelmintic in other countries. No published information is available about its excretion into breastmilk. Some information indicates that maternal use may be acceptable during breastfeeding. However, because there is little published experience with levamisole during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. The World Health Organization recommends against breastfeeding with maternal levamisole therapy.
◉ Effects in Breastfed Infants
A cohort of 33 infants who were breastfed (extent not stated) by hospitalized mothers taking nifurtimox was followed in the Democratic Republic of the Congo. Thirty mothers took a full course of 30 doses of oral nifurtimox 15 mg/kg daily and all received 14 doses of intravenous eflornithine 400 mg/kg daily for 7 days for human African trypanosomiasis. (sleeping sickness). Six nursing mothers also took levamisole. No serious adverse events were reported in any of the breastfed infants.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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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-tetrahydroimidazo[2,1-b][1,3]thiazole that has S configuration. It is used (generally as the monohydrochloride salt) to treat parasitic worm infections in pigs, sheep and cattle and was formerly used in humans as an adjuvant to chemotherapy for the treatment of various cancers. It is also widely used as an adulterant to coccaine. It has a role as an antinematodal drug, an antirheumatic drug, an immunomodulator, an immunological adjuvant and an EC 3.1.3.1 (alkaline phosphatase) inhibitor. It is an enantiomer of a dexamisole.
Levamisole is an antihelminthic drug that was commonly used for the treatment of parasitic, viral, and bacterial infections. It was manufactured by Janssen and first used in 1969 as an agent to treat worm infestations Levamisole was approved by the FDA in 1990 as an adjuvant treatment for colon cancer. Prior to this, levamisole was used as an antirheumatic therapy in the 1970s and 1980s for patients with rheumatoid arthritis. Because of its immunomodulatory effects, this drug has been studied in the treatment of various immune-mediated diseases, with some studies showing positive results. This drug has also been used in combination with other drugs for the treatment of various cancers. Levamisole was withdrawn from the American market in 2000 due to its ability to cause serious adverse effects, including agranulocytosis. Interestingly, levamisole has been found as an adulterant in cocaine and can lead to a variety of adverse effects in individuals using this drug.
Levamisole is an anthelmintic drug. Co-administered with fluorouracil in the treatment of Dukes' stage C colon cancer, levamisole restores immune function through stimulating antibody formation, enhancing T-cell activity, and potentiating macrophage function. (NCI04)
An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6)
See also: Levamisole Hydrochloride (has salt form); Levamisole Phosphate (has salt form); Doramectin; Levamisole (component of).

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Drug Indication
For adjuvant treatment in combination with fluorouracil after surgical resection in patients with Dukes' stage C colon cancer. Also used to treat malignant melanoma and head/neck cancer.

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Mechanism of Action
The mechanism of action of levamisole as an antiparasitic agent appears to be tied to its agnositic activity towards the L-subtype nicotinic acetylcholine receptors in nematode muscles. This agonistic action reduces the capacity of the males to control their reproductive muscles and limits their ability to copulate. The mechanism of action of Levamisole as an anticancer drug in combination with fluorouracil is unknown. The effects of levamisole on the immune system are complex. The drug appears to restore depressed immune function rather than to stimulate response to above-normal levels. Levamisole can stimulate formation of antibodies to various antigens, enhance T-cell responses by stimulating T-cell activation and proliferation, potentiate monocyte and macrophage functions including phagocytosis and chemotaxis, and increase neutrophil mobility, adherence, and chemotaxis.

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Pharmacodynamics
Levamisole is a synthetic imidazothiazole derivative that has been widely used in treatment of worm infestations in both humans and animals. As an anthelmintic, it probably works by targeting the nematode nicotinergic acetylcholine receptor. As an immunomodulator, it appears that Levamisole is an immunostimulant which has been shown to increase NK cells and activated T-cells in patients receiving this adjuvantly along with 5FU for Stage III colon cancer.

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.)