Levamisole
[CAS# 14769-73-4]

Identification

• Classification: API >> Antiparasitic drug >> Anthelmintic
• Name: Levamisole
• Synonyms: (S)-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1-b]thiazole
• Molecular Formula: C₁₁H₁₂N₂S
• Molecular Weight: 204.29
• CAS Registry Number: 14769-73-4
• EC Number: 238-836-5
• SMILES: C1CSC2=N[C@H](CN21)C3=CC=CC=C3

Properties

• Density: 1.3±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.713, Calc.^*
• Boiling Point: 344.4±45.0 ºC (760 mmHg), Calc.^*
• Flash Point: 162.1±28.7 ºC, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302
• Precautionary Statements: P264-P270-P301+P317-P330-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	3	H311
Specific target organ toxicity - repeated exposure	STOT RE	1	H372

Discovory and Applicatios

Levamisole is a synthetic compound that was originally developed in the 1960s as an anthelmintic drug for veterinary use. It was later found to have immunomodulatory properties, leading to its use in human medicine, particularly in the treatment of certain conditions such as colorectal cancer and as an adjunct in the treatment of rheumatoid arthritis.

Levamisole’s primary mode of action in veterinary medicine is as an anthelmintic agent. It works by interfering with the neuromuscular junctions in parasitic worms, causing paralysis and ultimately leading to the expulsion of the parasites from the host. As a result, levamisole was widely used in the treatment of worm infections in livestock and pets.

In human medicine, levamisole was first introduced in the 1970s for the treatment of colorectal cancer. It was used as an adjunct to chemotherapy, where it was believed to enhance the immune system's ability to fight cancer cells. The immunomodulatory effects of levamisole are attributed to its ability to enhance the function of T lymphocytes, which are critical in the body's immune response. Levamisole was often used in combination with other anticancer agents, such as fluorouracil, to improve the efficacy of treatment for colorectal cancer.

Levamisole’s use in the treatment of colorectal cancer, however, became less common in the 1980s due to concerns about side effects, including leukopenia (a decrease in white blood cells), which made it less preferable compared to other therapies. Despite this, levamisole continued to be used in some cases as a supportive agent in cancer treatment, particularly in certain regions where it remained accessible.

In addition to its use in cancer therapy, levamisole has also been employed in the treatment of rheumatoid arthritis. It was used to modulate the immune system and reduce the severity of the disease by influencing inflammatory pathways. However, its use in rheumatoid arthritis was also limited due to side effects, such as agranulocytosis, a severe reduction in white blood cells, which can increase the risk of infections.

Beyond its medical applications, levamisole has been reported as a contaminant in illicit drugs, particularly cocaine. In such cases, levamisole is often added to enhance the drug's effects, though it is not intended for human consumption and can lead to serious health issues, including skin necrosis and agranulocytosis.

The use of levamisole as an anthelmintic in humans has largely been replaced by other agents, and its application in cancer and autoimmune disorders has diminished over time due to the availability of more effective treatments with fewer side effects. Nevertheless, levamisole remains important in veterinary medicine and continues to be utilized in the treatment of parasitic infections in animals.

References

1991. Enhancement of in vitro lipopolysaccharide-stimulated interleukin-1 production by levamisole. Clinical Immunology and Immunopathology, 58(3).
DOI: 10.1016/0090-1229(91)90129-x

1986. Immunoregulatory treatment for minimal change nephrotic syndrome. Archives of Disease in Childhood, 61(2).
DOI: 10.1136/adc.61.2.153

1986. Anthelmintics for Cattle. The Veterinary clinics of North America. Food animal practice, 2(2).
DOI: 10.1016/s0749-0720(15)31259-7