Clinical data | |
---|---|
Trade names | Decaris, Ergamisol |
AHFS/Drugs.com | Micromedex Detailed Consumer Information |
MedlinePlus | a697011 |
License data |
|
Routes of administration | By mouth |
ATC code | |
Legal status | |
Legal status |
|
Pharmacokinetic data | |
Metabolism | Liver |
Elimination half-life | 3–4 hours |
Excretion | Kidney (70%) |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.035.290 |
Chemical and physical data | |
Formula | C11H12N2S |
Molar mass | 204.29 g·mol−1 |
3D model (JSmol) | |
Density | 1.31 g/cm3 |
Melting point | 60 °C (140 °F) |
Solubility in water | hydrochloride: 210 mg/mL (20 °C) |
| |
| |
(what is this?) (verify) |
Levamisole, sold under the brand name Ergamisol among others, is a medication used to treat parasitic worm infections, specifically ascariasis and hookworm infections. [1] It is taken by mouth. [2]
Side effects may include abdominal pain, vomiting, headache, and dizziness. [2] Use is not recommended during breastfeeding or the third trimester of pregnancy. [2] Serious side effects may include an increased risk of infection. [3] It belongs to the anthelmintic class of medications. [3]
Levamisole was invented in 1966 in Belgium by Janssen Pharmaceuticals. [4] It is on the World Health Organization's List of Essential Medicines. [5] Levamisole is also used as a dewormer for cattle. [6] [7]
Levamisole was originally used as an anthelmintic to treat worm infestations in both humans and animals. Levamisole works as a nicotinic acetylcholine receptor agonist that causes continued stimulation of the parasitic worm muscles, leading to paralysis. [8] Levamisole has gained prominence among aquarists as an effective treatment for Camallanus roundworm infestations in freshwater tropical fish. [9] Levamisole has been used to treat small ruminant animals since the late 1960s. [10] Levamisole-resistant parasitic worms are common in sheep farms in New Zealand, [11] Uruguay, [12] Paraguay, [13] and Brazil. [14]
Levamisole has been used to treat a variety of dermatologic conditions, including skin infections, leprosy, warts, lichen planus, and aphthous ulcers. [15]
An interesting side effect these reviewers reported in passing was "neurologic excitement". Later papers, from the Janssen group and others, indicate levamisole and its enantiomer, dexamisole, have some mood-elevating or antidepressant properties, although this was never a marketed use of the drug. [16] [17]
One of the more serious side effects of levamisole is agranulocytosis, or the depletion of the white blood cells. In particular, neutrophils appear to be affected the most. This occurs in 0.08–5% of the studied populations. [18]
It has been used as an adulterant in cocaine, resulting in serious side effects that present as levamisole induced necrosis syndrome, in which erythematous painful papules can appear almost anywhere on skin. [19] [20] [21]
Levamisole is readily absorbed from the gastrointestinal tract and metabolized in the liver. Its time to peak plasma concentration is 1.5–2 hours. The plasma elimination half-life is fairly quick at 3–4 hours which can contribute to not detecting levamisole intoxication. The metabolite half-life is 16 hours. Levamisole's excretion is primarily through the kidneys, with about 70% being excreted over 3 days. Only about 5% is excreted as unchanged levamisole. [22] [23]
Drug testing of racehorse urine has led to the revelation that among levamisole equine metabolites are both pemoline and aminorex, stimulants that are forbidden by racing authorities. [24] [25] [26] Further testing confirmed aminorex in human and canine urine, meaning that both humans and dogs also metabolize levamisole into aminorex, [27] though it is unclear whether plasma aminorex is present at any appreciable level. Blood samples following oral administration of levamisole out to 172 hr post-dose did not demonstrate any plasma aminorex levels above that of the limit of quantification (LoQ). Additionally, in cocaine-positive plasma samples, of which 42% contained levamisole, aminorex was never reported at concentrations higher than LoQ. [28]
Levamisole may be quantified in blood, plasma, or urine as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths involving adulterated street drugs. About 3% of an oral dose is eliminated unchanged in the 24-hour urine of humans. A post mortem blood levamisole concentration of 2.2 mg/L was present in a woman who died of a cocaine overdose. [29] [30]
Levamisole has increasingly been used as a cutting agent in cocaine sold around the globe with the highest incidence being in the United States. In 2008–2009, levamisole was found in 69% of cocaine samples seized by the Drug Enforcement Administration (DEA). [19] By April 2011, the DEA reported the adulterant was found in 82% of seizures. [31]
Levamisole adds bulk and weight to powdered cocaine (whereas other adulterants produce smaller "rocks" of cocaine) and makes the drug appear purer. [32] 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. [33]
Levamisole suppresses the production of white blood cells, 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. [19] [34] [35] Levamisole has also been linked to a risk of vasculitis, [36] and two cases of vasculitic skin necrosis have been reported in users of cocaine adulterated with levamisole. [37]
Levamisole-tainted cocaine has caused three deaths and sickened over 100 in US and Canada, as of 2009. [38]
The original synthesis at Janssen Pharmaceutica resulted in the preparation of a racemic mixture of two enantiomers, whose hydrochloride salt was reported to have a melting point of 264–265 °C; the free base of the racemate has a melting point of 87–89 °C. The racemic mixture is referred to as "tetramisole" - levamisole refers only to the levorotatory enantiomer of tetramisole.[ citation needed ]
Levamisole reversibly and uncompetitively inhibits most isoforms of alkaline phosphatase (e.g., human liver, bone, kidney, and spleen) except the intestinal and placental isoform. [40] [41] 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.[ citation needed ]
It is used to immobilize the nematode C. elegans on glass slides for imaging and dissection. [42]
In a C. elegans behavioral assay, analyzing the time course of paralysis provides information about the neuromuscular junction. Levamisole acts as an acetylcholine receptor agonist, which leads to muscle contraction. Continuing activation leads to paralysis. The time course of paralysis provides information about the acetylcholine receptors on the muscle. For example, mutants with fewer acetylcholine receptors may paralyze slower than wild type. [43]
It has been studied as a method to stimulate the immune system as part of the treatment of cancer. [44] It has also shown some efficacy in the treatment of nephrotic syndrome in children. [45]
After being pulled from the market in the US and Canada in 1999 and 2003, respectively, levamisole has been tested in combination with fluorouracil to treat colon cancer. Evidence from clinical trials support its addition to fluorouracil therapy to benefit patients with colon cancer. In some of the leukemic cell line studies, both levamisole and tetramisole showed similar effect. [46]
The combination doramectin/levamisole, sold under the brand name Valcor, is indicated for the treatment and control of gastrointestinal roundworms, lungworms, grubs, sucking lice, and mange mites in cattle. [6] It is given by subcutaneous injection. [6]
Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count and thus causing neutropenia in the circulating blood. It is a severe lack of one major class of infection-fighting white blood cells. People with this condition are at very high risk of serious infections due to their suppressed immune system.
Praziquantel (PZQ), sold under the brandname Biltricide among others, is a medication used to treat a number of types of parasitic worm infections in mammals, birds, amphibians, reptiles, and fish. In humans specifically, it is used to treat schistosomiasis, clonorchiasis, opisthorchiasis, tapeworm infections, cysticercosis, echinococcosis, paragonimiasis, fasciolopsiasis, and fasciolosis. It should not be used for worm infections of the eye. It is taken by mouth.
Ivermectin is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, it is used to treat infestations including head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis and lymphatic filariasis. It works through many mechanisms to kill the targeted parasites, and can be taken by mouth, or applied to the skin for external infestations. It belongs to the avermectin family of medications.
Haemonchus contortus, also known as the barber's pole worm, is a very common parasite and one of the most pathogenic nematodes of ruminants. Adult worms attach to abomasal mucosa and feed on the blood. This parasite is responsible for anemia, oedema, and death of infected sheep and goats, mainly during summer in warm, humid climates.
Ascaridia galli is a parasitic roundworm belonging to the phylum Nematoda. Nematodes of the genus Ascaridia are essentially intestinal parasites of birds. A. galli is the most prevalent and pathogenic species, especially in domestic fowl, Gallus domesticus. It causes ascaridiasis, a disease of poultry due to heavy worm infection, particularly in chickens and turkeys. It inhabits the small intestine, and can be occasionally seen in commercial eggs.
Egg hatch assay (EHA), also called an egg hatch test (EHT), is a method used to determine a given parasite's resistance to extant drug therapy.
4-Methylaminorex is a stimulant drug of the 2-amino-5-aryloxazoline class that was first synthesized in 1960 by McNeil Laboratories. It is also known by its street name "U4Euh" ("Euphoria"). It is banned in many countries as a stimulant.
Aminorex is a weight loss (anorectic) stimulant drug. It was withdrawn from the market after it was found to cause pulmonary hypertension. In the U.S., it is an illegal Schedule I drug, meaning it has high abuse potential, no accepted medical use, and a poor safety profile.
Emodepside is an anthelmintic drug that is effective against a number of gastrointestinal nematodes, is licensed for use in cats and belongs to the class of drugs known as the octadepsipeptides, a relatively new class of anthelmintic, which are suspected to achieve their anti-parasitic effect by a novel mechanism of action due to their ability to kill nematodes resistant to other anthelmintics.
Capillaria plica is a parasitic nematode which is most often found in the urinary bladder, and occasionally in the kidneys, of dogs and foxes. It has also been found in the domestic cat, and various wild mammals. Its presence usually produces no clinical symptoms, but in some cases, it leads to hematuria, cystitis, or difficulty in urination.
Thelaziasis is the term for infestation with parasitic nematodes of the genus Thelazia. The adults of all Thelazia species discovered so far inhabit the eyes and associated tissues of various mammal and bird hosts, including humans. Thelazia nematodes are often referred to as "eyeworms".
Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may also be called vermifuges or vermicides. Anthelmintics are used to treat people who are infected by helminths, a condition called helminthiasis. These drugs are also used to treat infected animals, particularly small ruminants such as goats and sheep.
Oxfendazole is a broad spectrum benzimidazole anthelmintic. Its main use is for protecting livestock against roundworm, strongyles and pinworms. Oxfendazole is the sulfoxide metabolite of fenbendazole.
Teladorsagia circumcincta is a nematode that is one of the most important parasites of sheep and goats. It was previously known as Ostertagia circumcincta and is colloquially known as the brown stomach worm. It is common in cool, temperate areas, such as south-eastern and south-western Australia and the United Kingdom. There is considerable variation among lambs and kids in susceptibility to infection. Much of the variation is genetic and influences the immune response. The parasite induces a type I hypersensitivity response which is responsible for the relative protein deficiency which is characteristic of severely infected animals. There are mechanistic mathematical models which can predict the course of infection. There are a variety of ways to control the infection and a combination of control measures is likely to provide the most effective and sustainable control.
Levamisole induced necrosis syndrome (LINES) is a complication of adulterated cocaine recognized in 2011, caused by the use of levamisole as a cutting agent for cocaine. Spontaneous bruising of the earlobes is considered characteristic of this condition, but lesions can present anywhere on the body.
Amphistomiasis is a parasitic disease of livestock animals, more commonly of cattle and sheep, and humans caused by immature helminthic flatworms belonging to the order Echinostomida. The term amphistomiasis is used for broader connotation implying the disease inflicted by members of Echinostomida including the family Paramphistomidae/Gastrodiscidae ; whereas paramphistomiasis is restricted to that of the members of the family Paramphistomidae only. G. discoides and Watsonius watsoni are responsible for the disease in humans, while most paramphistomes are responsible in livestock animals, and some wild mammals. In livestock industry the disease causes heavy economic backlashes due to poor production of milk, meat and wool.
Cooperia oncophora is one of the most common intestinal parasitic nematodes in cattle in temperate regions. Infections with C. oncophora may result in mild clinical symptoms, but can lead to weight loss and damage of the small intestine, especially when co-infections with other nematodes such as O. ostertagi occur. Infections are usually treated with broad-spectrum anthelmintics such as benzimidazole, but resistance to these drugs has developed in the last decades and is now very common. C. oncophora has a direct life cycle. Infective larvae are ingested by the host. The larvae grow to adults, which reproduce in the small intestines. Eggs are shed onto the pasture with the faeces, which leads to new infections. Co-infections with other gastro-intestinal nematodes such as O. ostertagi and H. contortus are common.
The fecal egg count reduction test was suggested in the World Association for the Advancement of Veterinary Parasitology guideline for estimating the reduction in fecal egg counts and its corresponding confidence interval. The results of this test can be used to determine the anthelmintic resistance status of the animals.
Carlos E. Lanusse is an Argentine scientist and a professor of Pharmacology. He is the Director of the Veterinary Research Center and the Science and Technology Center of the Argentina National Council of Research in Tandil.
Monepantel is an anthelmintic approved for use in sheep and cattle to control gastrointestinal nematodes. It belongs to a new class of anthelmintics called aminoacetonitrile derivatives (AAD). It is marketed by Elanco as Zolvix as a single active, or Zolvix Plus in combination with the macrocyclic lactone abamectin.