Levamisole
Encyclopedia
Levamisole is an anthelminthic and immunomodulator
belonging to a class of synthetic imidazothiazole derivatives. It was discovered at Janssen Pharmaceutica
in 1966. Levamisole has been used in humans to treat parasitic worm
infections, and has been studied in combination with other forms of chemotherapy
for colon cancer, melanoma
, and head and neck cancer
. The drug was withdrawn from the U.S. and Canadian markets in 2000 and 2003 respectively, due to the risk of serious side effects and the availability of more effective replacement medications. The key side toxic effect of the drug is agranulocytosis
, a severe depletion of white blood cells that leaves patients vulnerable to infection.
Currently, levamisole remains in veterinary
use as a dewormer for livestock. The medication has also been increasingly used as an adulterant
in cocaine
sold in the U.S. and Canada, resulting in serious side effects.
in cattle, pigs, and sheep. However, levamisole has also gained prominence among aquarists as an effective treatment for Camallanus roundworm infestations in freshwater tropical fish.
Levamisole has been tested in combination with fluorouracil
to treat colon cancer. There is no good evidence from clinical trials that its addition to fluorouracil therapy benefits patients with colon cancer, and it is no longer used for this. Levamisole is also used infrequently to treat melanoma
and head and neck cancer
. It is unclear from its mechanism of action why it would have an effect in treating colon cancer, although it has been shown to have "immune-stimulating" properties in some situations.
A 1984 study on complicated influenza
found levamisole to be an effective inducer of interferon
and recommended its use in combination therapy for influenza. It is also used routinely in India
to treat steroid
-dependent childhood nephrotic syndrome
cases, based on literature published in a few U.K.-based studies. Levamisole has been used to treat a variety of dermatologic conditions, including skin infections, leprosy
, warts, lichen planus
, and aphthous ulcer
s.
most isoforms of alkaline phosphatase
(e.g. human liver, bone, kidney, and spleen) except the intestinal and placental isoform. It is thus used as an inhibitor along with substrate to reduce background alkaline phosphatase activity in biomedical assays involving detection signal amplification by intestinal alkaline phosphatase, for example in in situ hybridization
or Western blot
protocols.
In addition, it is used to immobilize the nematode C. elegans
on glass slides for imaging.
in cocaine
sold in the U.S. and Canada. In 2008–2009, levamisole was found in 69% of cocaine samples seized by the U.S. Drug Enforcement Administration
(DEA). By April 2011, the DEA reported that the adulterant was found in 82% of seizures.
Levamisole adds bulk and weight to powdered cocaine
(whereas other adulterants produce smaller "rocks" of cocaine) and makes the drug appear more pure. In a series of investigative articles for The Stranger
, Brendan Kiley details other rationales for levamisole's rise as an adulterant: possible stimulant effects, a similar appearance to cocaine, and an ability to pass street purity tests.
Levamisole suppresses the production of white blood cell
s, resulting in neutropenia
and agranulocytosis
. With the increasing use of levamisole as an adulterant
, a number of these complications have been reported among cocaine users. Levamisole has also been linked to a risk of vasculitis
, and 2 cases of vasculitic skin necrosis have been reported in users of cocaine adulterated with levamisole.
Levamisole-tainted cocaine was linked to several high-profile deaths. Toxicology reports showed that levamisole, along with cocaine, was present in DJ AM's body at the time of his death. Andrew Koppel, son of newsman Ted Koppel
, was also found with Levamisole in his body after his death was ruled a drug overdose.
Immunomodulator
An immunomodulator, also known as an immunotherapy is a substance which has an effect on the immune system.- Immunosuppressants :Inhibits immune response in organ transplantation and autoimmune diseases.- Immunostimulants :...
belonging to a class of synthetic imidazothiazole derivatives. It was discovered at Janssen Pharmaceutica
Janssen Pharmaceutica
Janssen Pharmaceutica is pharmaceutical company, established in Belgium in 1953 by Paul Janssen. Its headquarters are located in Beerse, in the Campine region of the province of Antwerp, Belgium. It was created not as a subsidiary of a chemical factory but solely with the aim of conducting...
in 1966. Levamisole has been used in humans to treat parasitic worm
Parasitic worm
Parasitic worms or helminths are a division of eukaryoticparasites that, unlike external parasites such as lice and fleas, live inside their host. They are worm-like organisms that live and feed off living hosts, receiving nourishment and protection while disrupting their hosts' nutrient...
infections, and has been studied in combination with other forms of chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
for colon cancer, melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
, and head and neck cancer
Head and neck cancer
Head and neck cancer refers to a group of biologically similar cancers that start in the upper aerodigestive tract, including the lip, oral cavity , nasal cavity , paranasal sinuses, pharynx, and larynx. 90% of head and neck cancers are squamous cell carcinomas , originating from the mucosal lining...
. The drug was withdrawn from the U.S. and Canadian markets in 2000 and 2003 respectively, due to the risk of serious side effects and the availability of more effective replacement medications. The key side toxic effect of the drug is agranulocytosis
Agranulocytosis
Granulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
, a severe depletion of white blood cells that leaves patients vulnerable to infection.
Currently, levamisole remains in veterinary
Veterinary medicine
Veterinary Medicine is the branch of science that deals with the prevention, diagnosis and treatment of disease, disorder and injury in non-human animals...
use as a dewormer for livestock. The medication has also been increasingly used as an adulterant
Adulterant
An adulterant is a chemical substance which should not be contained within other substances for legal or other reasons. Adulterants may be intentionally added to more expensive substances to increase visible quantities and reduce manufacturing costs or for some other deceptive or malicious purpose...
in cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
sold in the U.S. and Canada, resulting in serious side effects.
Medical uses
Levamisole was originally used as an anthelminthic to treat worm infestations in both humans and animals. Most current commercial preparations are intended for veterinary use as a dewormerDeworming
Deworming is the giving of an anthelmintic drug to an animal to rid it of intestinal parasites, such as roundworm and tapeworm...
in cattle, pigs, and sheep. However, levamisole has also gained prominence among aquarists as an effective treatment for Camallanus roundworm infestations in freshwater tropical fish.
Levamisole has been tested in combination with fluorouracil
Fluorouracil
Fluorouracil is a drug that is a pyrimidine analog which is used in the treatment of cancer. It is a suicide inhibitor and works through irreversible inhibition of thymidylate synthase. It belongs to the family of drugs called antimetabolites...
to treat colon cancer. There is no good evidence from clinical trials that its addition to fluorouracil therapy benefits patients with colon cancer, and it is no longer used for this. Levamisole is also used infrequently to treat melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
and head and neck cancer
Head and neck cancer
Head and neck cancer refers to a group of biologically similar cancers that start in the upper aerodigestive tract, including the lip, oral cavity , nasal cavity , paranasal sinuses, pharynx, and larynx. 90% of head and neck cancers are squamous cell carcinomas , originating from the mucosal lining...
. It is unclear from its mechanism of action why it would have an effect in treating colon cancer, although it has been shown to have "immune-stimulating" properties in some situations.
A 1984 study on complicated influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
found levamisole to be an effective inducer of interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
and recommended its use in combination therapy for influenza. It is also used routinely in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
to treat steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
-dependent childhood nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
cases, based on literature published in a few U.K.-based studies. Levamisole has been used to treat a variety of dermatologic conditions, including skin infections, leprosy
Leprosy
Leprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...
, warts, lichen planus
Lichen planus
Lichen planus is a chronic mucocutaneous disease that affects the skin, tongue, and oral mucosa. The disease presents itself in the form of papules, lesions, or rashes. Lichen planus does not involve lichens, the fungus/algae symbionts that often grow on tree trunks; the name refers to the dry and...
, and aphthous ulcer
Aphthous ulcer
An aphthous ulcer , also known as a canker sore, is a type of mouth ulcer which presents as a painful open sore inside the mouth or upper throat characterized by a break in the mucous membrane. Its cause is unknown, but they are not contagious...
s.
Laboratory use
Levamisole reversibly and non-competitively inhibitsNon-competitive inhibition
Non-competitive inhibition is a type of enzyme inhibition where the inhibitor reduces the activity of the enzyme, by binding not to the active site on the enzyme, but to a different site...
most isoforms of alkaline phosphatase
Alkaline phosphatase
Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...
(e.g. human liver, bone, kidney, and spleen) except the intestinal and placental isoform. It is thus used as an inhibitor along with substrate to reduce background alkaline phosphatase activity in biomedical assays involving detection signal amplification by intestinal alkaline phosphatase, for example in in situ hybridization
In situ hybridization
In situ hybridization is a type of hybridization that uses a labeled complementary DNA or RNA strand to localize a specific DNA or RNA sequence in a portion or section of tissue , or, if the tissue is small enough , in the entire tissue...
or Western blot
Western blot
The western blot is a widely used analytical technique used to detect specific proteins in the given sample of tissue homogenate or extract. It uses gel electrophoresis to separate native proteins by 3-D structure or denatured proteins by the length of the polypeptide...
protocols.
In addition, it is used to immobilize the nematode C. elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
on glass slides for imaging.
Illicit use
Levamisole has increasingly been used as a cutting agentCutting agent
A cutting agent is a chemical used to "cut" illicit drugs with something less expensive than the drug itself.-Overview:The classical model of drug cutting A cutting agent is a chemical used to "cut" (dilute) illicit drugs with something less expensive than the drug itself.-Overview:The classical...
in cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
sold in the U.S. and Canada. In 2008–2009, levamisole was found in 69% of cocaine samples seized by the U.S. Drug Enforcement Administration
Drug Enforcement Administration
The Drug Enforcement Administration is a federal law enforcement agency under the United States Department of Justice, tasked with combating drug smuggling and use within the United States...
(DEA). By April 2011, the DEA reported that the adulterant was found in 82% of seizures.
Levamisole adds bulk and weight to powdered cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
(whereas other adulterants produce smaller "rocks" of cocaine) and makes the drug appear more pure. In a series of investigative articles for The Stranger
The Stranger (newspaper)
The Stranger is an alternative weekly newspaper in Seattle, Washington, USA. It runs a blog known as Slog.-History:The Stranger was founded by Tim Keck, who had previously co-founded the satirical newspaper The Onion, and cartoonist James Sturm. Its first issue came out on September 23, 1991...
, Brendan Kiley details other rationales for levamisole's rise as an adulterant: possible stimulant effects, a similar appearance to cocaine, and an ability to pass street purity tests.
Levamisole suppresses the production of white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s, resulting in neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
and agranulocytosis
Agranulocytosis
Granulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
. With the increasing use of levamisole as an adulterant
Adulterant
An adulterant is a chemical substance which should not be contained within other substances for legal or other reasons. Adulterants may be intentionally added to more expensive substances to increase visible quantities and reduce manufacturing costs or for some other deceptive or malicious purpose...
, a number of these complications have been reported among cocaine users. Levamisole has also been linked to a risk of vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
, and 2 cases of vasculitic skin necrosis have been reported in users of cocaine adulterated with levamisole.
Levamisole-tainted cocaine was linked to several high-profile deaths. Toxicology reports showed that levamisole, along with cocaine, was present in DJ AM's body at the time of his death. Andrew Koppel, son of newsman Ted Koppel
Ted Koppel
Edward James "Ted" Koppel is an English-born American broadcast journalist, best known as the anchor for Nightline from the program's inception in 1980 until his retirement in late 2005. After leaving Nightline, Koppel worked as managing editor for the Discovery Channel before resigning in 2008...
, was also found with Levamisole in his body after his death was ruled a drug overdose.