Niclosamide, sold under the brand name Niclocide among others, is an

anthelmintic 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 ...

medication used to treat

tapeworm Eucestoda, commonly referred to as tapeworms, is the larger of the two subclasses of flatworms in the class Cestoda (the other subclass is Cestodaria). Larvae have six posterior hooks on the scolex (head), in contrast to the ten-hooked Cesto ...

infestations, including

diphyllobothriasis Diphyllobothriasis is the infection caused by tapeworms of the genus ''Diphyllobothrium'' (commonly '' D. latum'' and ''D. nihonkaiense''). Diphyllobothriasis mostly occurs in regions where raw fish is regularly consumed; those who consume raw fi ...

, hymenolepiasis, and

taeniasis Taeniasis is an infection within the intestines by adult tapeworms belonging to the genus '' Taenia''. There are generally no or only mild symptoms. Symptoms may occasionally include weight loss or abdominal pain. Segments of tapeworm may be ...

. It is not effective against other worms such as flukes or

roundworms The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a broa ...

. It is taken by mouth. Side effects include nausea, vomiting, abdominal pain, and itchiness. It may be used during pregnancy. It works by blocking glucose uptake and

oxidative phosphorylation Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine t ...

by the worm. Niclosamide was first synthesized in 1958. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. Niclosamide is not available for human use in the United States.

Side effects

Side effects include nausea, vomiting, abdominal pain,

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel moveme ...

, and itchiness. Rarely, dizziness, skin rash, drowsiness, perianal itching, or an unpleasant taste occur. For some of these reasons,

praziquantel 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 sc ...

is a preferable and equally effective treatment for tapeworm infestation. Important Note: Niclosamide kills the pork tapeworm and results in its digestion. This then may cause a multitude of viable eggs to be released and may result in

cysticercosis Cysticercosis is a tissue infection caused by the young form of the pork tapeworm. People may have few or no symptoms for years. In some cases, particularly in Asia, solid lumps of between one and two centimetres may develop under the skin. Aft ...

. Therefore, a purge should be given 1 or two hours after treatment. CNS cysticercosis is a life-threatening condition and may require brain surgery.

Mechanism of action

Niclosamide inhibits

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

uptake, oxidative

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

, and anaerobic metabolism in the tapeworm.

Other applications

Niclosamide's metabolic effects are relevant to wide ranges of organisms, and accordingly it has been applied as a control measure to organisms other than tapeworms. For example, it is an active ingredient in some formulations such as Bayluscide for killing

lamprey Lampreys (sometimes inaccurately called lamprey eels) are an ancient extant lineage of jawless fish of the order Petromyzontiformes , placed in the superclass Cyclostomata. The adult lamprey may be characterized by a toothed, funnel-like s ...

larvae, as a molluscide, and as a general purpose piscicide in aquaculture. Niclosamide has a short half-life in water in field conditions; this makes it valuable in ridding commercial fish ponds of unwanted fish; it loses its activity soon enough to permit re-stocking within a few days of eradicating the previous population. Researchers have found that niclosamide is effective in killing invasive

zebra mussel The zebra mussel (''Dreissena polymorpha'') is a small freshwater mussel. The species originates from the lakes of southern Russia and Ukraine, but has been accidentally introduced to numerous other areas and has become an invasive species in ma ...

s in cool waters.

Research

Niclosamide is being studied in a number of types of cancer. Niclosamide along with oxyclozanide, another anti-

drug, was found in a 2015 study to display "strong ''in vivo'' and ''in vitro'' activity against methicillin-resistant ''Staphylococcus aureus'' (MRSA)". Various studies have shown that Niclosamide has the potential to counteract various viral infections, at least in experimental conditions. For instance, it has been shown that it impairs the replication of

Hepatitis E Hepatitis E is inflammation of the liver caused by infection with the hepatitis E virus (HEV); it is a type of viral hepatitis. Hepatitis E has mainly a fecal-oral transmission route that is similar to hepatitis A, although the viruses are unrel ...

virus. On July 1, 2020, Danish biotech company UNION started a clinical study using niclosamide in the treatment of

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quick ...

. Another study demonstrated the benefit of a combination of Niclosamide and

ivermectin Ivermectin (, '' EYE-vər-MEK-tin'') 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, today it is used to treat i ...

against SARS-CoV-2 activity, showing a synergistic profile, suggesting this combination should be further tested in clinical trials. There is another study that investigated the use of niclosamide as a treatment for COVID-19, showing effectiveness against virus replication and associated cytopathicity. In 2018, niclosamide was observed to be a potent activator of PTEN-induced kinase 1 in primary cortical neurons. As PINK1 dysfunction is associated with a form of

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...

, this quality makes niclosamide and derivative compounds attractive as research tools and potential treatment avenues for the condition.

References

External links

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