Oxamniquine, sold under the brand name Vansil among others, is a medication used to treat schistosomiasis due to '' Schistosoma mansoni''.

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 ...

, however, is often the preferred treatment. It is given

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

and used as a single dose. Common side effects include sleepiness, headache, nausea,

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

, and reddish urine. It is typically not recommended during

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

, if possible.

Seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

may occur and therefore caution is recommended in people with

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

. It works by causing paralysis of the

parasitic worms Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other parasitic worms such as sc ...

. It is in the

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 ...

family of medications. Oxamniquine was first used medically in 1972. 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 ...

. It is not commercially available in the United States. It is more expensive than praziquantel.

Medical uses

Oxamniquine is used for treatment of schistosomiasis. According to one systematic review,

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 the standard treatment for '' S. mansoni'' infections and oxamniquine also appears effective.

Side effects

It is generally well tolerated following oral doses. Dizziness with or without drowsiness occurs in at least a third of patients, beginning up to three hours after a dose, and usually lasts for up to six hours. Headache and gastrointestinal effects, such as nausea, vomiting, and diarrhoea, are also common. Allergic-type reactions, including urticaria, pruritic skin rashes, and fever, may occur. Liver enzyme values have been raised transiently in some patients. Epileptiform convulsions have been reported, especially in patients with a history of convulsive disorders. Hallucinations and excitement have occurred rarely. A reddish discoloration of urine, probably due to a metabolite of oxamniquine, has been reported. Oxamniquine is not recommended during pregnancy.

Pharmacokinetics

Peak plasma concentrations are achieved one to three hours after a dose, and the plasma half-life is 1.0 to 2.5 hours. It is extensively metabolised to inactive metabolites, principally the 6-carboxy derivative, which are excreted in the urine. About 70% of a dose of oxamniquine is excreted as the 6-carboxy metabolite within 12 hours of a dose; traces of the 2-carboxy metabolite have also been detected in the urine.

Mechanism of action

It is an

with schistosomicidal activity against '' Schistosoma mansoni'', but not against other ''Schistosoma'' spp. Oxamniquine is a potent single-dose agent for treatment of ''S. mansoni'' infection, and it causes worms to shift from the

mesenteric The mesentery is an organ that attaches the intestines to the posterior abdominal wall in humans and is formed by the double fold of peritoneum. It helps in storing fat and allowing blood vessels, lymphatics, and nerves to supply the intestine ...

veins to the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

, where the male worms are retained; the female worms return to the mesentery, but can no longer release eggs.Martidale, ''The Extra Pharmacopoeia'', 31st ed, p121 Oxamniquine is a semisynthetic tetrahydroquinoline and possibly acts by DNA binding, resulting in contraction and paralysis of the worms and eventual detachment from terminal

venules A venule is a very small blood vessel in the microcirculation that allows blood to return from the capillary beds to drain into the larger blood vessels, the veins. Venules range from 7μm to 1mm in diameter. Veins contain approximately 70% of ...

in the mesentry, and death. Its biochemical mechanisms are hypothesized to be related to an anticholinergic effect, which increases the parasite's motility, as well as inhibiting the synthesis of nucleic acids. Oxamniquine acts mainly on male worms, but also induces small changes on a small proportion of females. Like

, it promotes more severe damage of the dorsal tegument than of the ventral surface. The drug causes the male worms to shift from the mesenteric circulation to the liver, where the cellular host response causes its final elimination. The changes caused in the females are reversible and are due primarily to the discontinued male stimulation rather than the direct effect of oxamniquine.

History

Oxamniquine was first described by Kaye and Woolhouse in 1972 as a metabolite of the compound UK 3883 (2-isopropylaminomethyl-6-methyl-7-nitro-1,2,3,4-tetrahydroquinoline). Initially, it was prepared by enzymatic hydroxylation via the fungus '' Aspergillus sclerotiorum''. In 1979,

Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...

Sandwich A sandwich is a food typically consisting of vegetables, sliced cheese or meat, placed on or between slices of bread, or more generally any dish wherein bread serves as a container or wrapper for another food type. The sandwich began as a po ...

was presented with the

Queen's Award for Technological Achievement Queens is a borough of New York City. Queens or Queen's may also refer to: Arts and entertainment * Queens (group), a Polish musical group * "Queens" (Saara Aalto song), 2018 * ''Queens'' (novel), by Stephen Pickles, 1984 * "Queens", a song by C ...

in recognition of the outstanding contribution made to tropical medicine by MANSIL (oxamniquine).

Brand names

* Vansil; (Pfizer) 250 mg capsules, syrup 250 mg/5 mL * Mansil; 250 mg Tablets

Stereochemistry

Oxamniquine contains a stereocenter and consists of two enantiomers. This is a

racemate In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

, i.e. a 1: 1 mixture of ('' R '') - and the ('' S '') - form:

References

* AHFS Database

External links

Drugs.com

* {{portal bar, Medicine Antiparasitic agents Isopropyl compounds Nitro compounds Primary alcohols Tetrahydroquinolines World Health Organization essential medicines Wikipedia medicine articles ready to translate