Niclosamide is an established pharmaceutical compound that has been used globally for decades to treat parasitic infections in humans. It belongs to the salicylanilide class of pharmacological agents. Niclosamide has been included on the World Health Organization’s list of essential medicines due to its effectiveness and has a long history of safe use.
Treating Parasitic Infections
Niclosamide is used as an anthelminthic agent to treat parasitic worm infections, specifically targeting intestinal tapeworms (cestodes). It is highly effective against several species and is a first-line treatment for infections caused by:
- Beef tapeworm (Taenia saginata)
- Pork tapeworm (Taenia solium)
- Broad or fish tapeworm (Diphyllobothrium latum)
- Dwarf tapeworm (Hymenolepis nana), although this requires a longer dosage regimen.
The drug works by killing the adult tapeworm on contact within the gastrointestinal tract. Niclosamide is generally not effective against other types of parasitic worms, such as pinworms or roundworms. For pork tapeworm infections, a separate laxative may be given after treatment to help expel the dead worm.
How Niclosamide Works
The effect of niclosamide on tapeworms stems from its action as an uncoupler of oxidative phosphorylation within the parasite’s mitochondria. Oxidative phosphorylation is the process cells use to generate adenosine triphosphate (ATP), the primary molecule for cellular energy. Niclosamide disrupts the parasite’s ability to produce this energy.
The drug acts as a protonophore, allowing protons to pass freely across the inner mitochondrial membrane. This bypasses the ATP synthase enzyme, which is responsible for synthesizing ATP. The failure to synthesize ATP rapidly depletes the parasite’s energy supply, leading to paralysis and death. Because the drug has minimal absorption into the human bloodstream, human cells, which also rely on oxidative phosphorylation, are largely unaffected by systemic toxicity.
Investigational Uses and Repurposing
Niclosamide has generated significant scientific interest for its potential in treating a variety of other human diseases, leveraging its known safety profile for new applications. The drug’s broad activity is linked to its ability to modulate several cellular signaling pathways, in addition to its mitochondrial effects.
Cancer Therapy
A major area of investigation is in cancer therapy, where niclosamide has demonstrated preclinical activity against a wide range of cancer cells. It has been shown to inhibit pathways like Wnt/\(\beta\)-catenin, mTORC1, and STAT3, which are frequently overactive in tumor growth and survival. Niclosamide can induce cancer cell death by regulating metabolic pathways.
Antiviral Applications
The drug has also shown promise in antiviral applications against various pathogens. Studies have indicated that niclosamide may be effective against certain RNA viruses, including:
- Coronaviruses like SARS-CoV
- MERS-CoV
- Zika virus
- Chikungunya virus
Metabolic Disorders
Furthermore, niclosamide is being investigated for metabolic disorders, including conditions like Type II diabetes and non-alcoholic fatty liver disease (NAFLD). Its ability to affect cellular metabolism through mitochondrial uncoupling suggests a potential role in improving metabolic health. All these applications—in cancer, antiviral, and metabolic treatment—are currently investigational and not yet approved for clinical use.
Patient Safety and Dosage Guidelines
Niclosamide is administered orally as chewable tablets. For optimal effect, the tablets should be thoroughly chewed or crushed before being swallowed with a small amount of water. If the medication is given to a child, the tablet is often crushed into a fine powder and mixed with water to form a paste.
The dosage varies significantly depending on the type of tapeworm infection being treated and the patient’s body weight. For beef or fish tapeworms, a single two-gram dose is generally sufficient for adults. However, dwarf tapeworm infections require a multi-day course of treatment, typically involving a higher initial dose followed by smaller daily doses for about seven days.
Common side effects are usually mild and confined to the gastrointestinal tract, including mild nausea, vomiting, or abdominal pain. Patients are advised to take the medication after a light meal to help prevent stomach upset. Contraindications generally include known hypersensitivity to the drug. Patients are typically advised to avoid alcohol consumption during treatment, and follow-up testing is often required to confirm that the parasitic infection has been fully cleared.