Levamisole hydrochloride
[CAS# 16595-80-5]

Identification

• Classification: API >> Antiparasitic drug >> Anthelmintic
• Name: Levamisole hydrochloride
• Synonyms: (-)-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1-b]thiazole hydrochloride
• Molecular Formula: C₁₁H₁₂N₂S.HCl
• Molecular Weight: 240.75
• CAS Registry Number: 16595-80-5
• EC Number: 240-654-6
• SMILES: C1CSC2=N[C@H](CN21)C3=CC=CC=C3.Cl

Properties

• Solubility: 25 mg/mL (DMSO), 10 mg/mL (ethanol), 20mg/mL (DMF) (Expl.)
• Melting point: 228-230 °C (Expl.)
• alpha: -128 ° (c=5, H2O)

Safety Data

• Hazard Symbols: GHS06;GHS08 Danger
• Risk Statements: H301-H361-H373-H412
• Safety Statements: P203-P260-P264-P270-P273-P280-P301+P316-P318-P319-P321-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Reproductive toxicity	Repr.	2	H361
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Germ cell mutagenicity	Muta.	2	H341
Skin sensitization	Skin Sens.	1	H317
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	3	H331
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315

• Transport Information: UN 2811

Discovery and Applications

Levamisole hydrochloride is a synthetic anthelmintic and immunomodulatory drug that was first developed in the 1960s by the pharmaceutical company Merck. It was initially introduced for the treatment of parasitic worm infections in humans and animals. The compound is a derivative of imidazothiazole and is known for its effectiveness against a variety of helminths (parasitic worms), including those responsible for conditions like ascariasis, hookworm, and strongyloidiasis.

The primary mechanism of action of levamisole hydrochloride is the stimulation of nicotinic acetylcholine receptors on the neuromuscular junction of the helminths. This leads to paralysis and subsequent expulsion of the worms from the host's gastrointestinal tract. The drug has a broad spectrum of activity against different types of parasitic worms, making it a useful tool in the treatment of various parasitic infections.

Levamisole hydrochloride was once widely used in veterinary medicine to control parasitic infections in livestock and pets. In human medicine, it has been used to treat conditions such as roundworm infections and hookworm diseases. Its use in humans has been largely phased out for anthelmintic purposes due to the development of more effective and less toxic alternatives. However, levamisole remains an important drug in veterinary medicine and is still used to treat parasitic infections in animals.

In addition to its anthelmintic activity, levamisole hydrochloride has been found to have immunomodulatory effects. It can stimulate the immune system, particularly by enhancing the activity of T-helper cells and increasing the production of certain cytokines. This immunostimulatory property led to its use in the treatment of conditions such as rheumatoid arthritis, where it was used as an adjunct therapy to improve immune function. However, its use in autoimmune diseases has decreased due to concerns about side effects and the availability of more effective immunosuppressive drugs.

Levamisole hydrochloride has also been used in cancer therapy, particularly in combination with other chemotherapy agents. It was explored as an adjunct treatment for colorectal cancer, where it was thought to boost the immune response to tumor cells. However, the results of clinical trials were mixed, and its use in cancer treatment is now limited.

In recent years, levamisole hydrochloride has gained attention due to its association with illicit drug use. It has been found as an adulterant in cocaine, where it is added to enhance the weight and appearance of the drug. This practice has raised public health concerns, as the presence of levamisole in illicit drugs can lead to serious side effects, including agranulocytosis (a condition where white blood cell counts drop significantly), which can be life-threatening.

Levamisole hydrochloride is generally well tolerated when used as prescribed, but it can cause side effects such as gastrointestinal disturbances, headaches, dizziness, and skin rashes. Serious side effects, although rare, can include immune system suppression, agranulocytosis, and liver toxicity. Monitoring of blood counts and liver function is recommended during prolonged use of the drug to mitigate the risk of these adverse effects.

In summary, levamisole hydrochloride is a versatile drug with both anthelmintic and immunomodulatory properties. It has been widely used in the treatment of parasitic infections in both humans and animals, though its use in human medicine has decreased in favor of newer therapies. The drug's immunomodulatory effects have been explored for the treatment of autoimmune diseases and cancer, but its use in these areas has been limited. The discovery and application of levamisole hydrochloride have had a significant impact on the management of parasitic diseases, though its association with illicit drug use has raised concerns in recent years.

References

1979. Interaction between levamisole and aspirin in man. British Journal of Clinical Pharmacology, 7(6).
DOI: 10.1111/j.1365-2125.1979.tb04657.x

1979. The effect of levamisole on postoperative immunosuppression. The British Journal of Surgery, 66(7).
DOI: 10.1002/bjs.1800660717

1979. Levamisole in the treatment of cyclical neutropenia. Postgraduate Medical Journal, 55(642).
DOI: 10.1136/pgmj.55.642.279```