Chemistry:Oxamniquine
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| Trade names | Vansil |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | Readily absorbed when taken by mouth |
| Metabolism | liver |
| Elimination half-life | 1 to 2.5h |
| Excretion | mainly in urine |
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| Chemical and physical data | |
| Formula | C14H21N3O3 |
| Molar mass | 279.3 g·mol−1 |
| 3D model (JSmol) | |
| Chirality | Racemic mixture |
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Oxamniquine, sold under the brand name Vansil among others, is a medication used to treat schistosomiasis due to Schistosoma mansoni.[1] Praziquantel, however, is often the preferred treatment.[2] It is given by mouth and used as a single dose.[2]
Common side effects include sleepiness, headache, nausea, diarrhea, and reddish urine.[1] It is typically not recommended during pregnancy, if possible.[1] Seizures may occur and therefore caution is recommended in people with epilepsy.[1] It works by causing paralysis of the parasitic worms.[3] It is in the anthelmintic family of medications.[4]
Oxamniquine was first used medically in 1972.[5] It is on the World Health Organization's List of Essential Medicines.[6] It is not commercially available in the United States.[4] It is more expensive than praziquantel.[7]
Medical uses
Oxamniquine is used for treatment of schistosomiasis. According to one systematic review, praziquantel is the standard treatment for S. mansoni infections and oxamniquine also appears effective.[8]
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.[citation needed]
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.[citation needed]
A reddish discoloration of urine, probably due to a metabolite of oxamniquine, has been reported.[citation needed]
Oxamniquine is not recommended during pregnancy.[1]
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.[citation needed]
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 anthelmintic 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 veins to the liver, where the male worms are retained; the female worms return to the mesentery, but can no longer release eggs.[9]
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 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 praziquantel, 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.[citation needed]
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 at Sandwich was presented with the Queen's Award for Technological Achievement in recognition of the outstanding contribution made to tropical medicine by MANSIL (oxamniquine).[citation needed]
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, i.e. a 1: 1 mixture of ( R ) - and the ( S ) - form:
| Enantiomers of oxamniquine | |
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-Oxamniquin_Structural_Formula_V1.svg) (R)-isomer |
-Oxamniquin_Structural_Formula_V1.svg) (S)-isomer |
References
- ↑ 1.0 1.1 1.2 1.3 1.4 WHO Model Formulary 2008. World Health Organization. 2009. p. 94. ISBN 978-9-2415-4765-9.
- ↑ 2.0 2.1 "Helminthic Diseases: Schistosomiasis" (in en). Public Health and Infectious Diseases. Elsevier. 2010. p. 351. ISBN 978-0-12-381507-1. https://books.google.com/books?id=bjcycxFpqEwC&pg=PA351.
- ↑ "Antiparasitic Agents" (in en). Infectious Diseases (4th ed.). Elsevier Health Sciences. 2016. p. 1371. ISBN 978-0-7020-6338-1. https://books.google.com/books?id=Dhq3DAAAQBAJ&pg=PA1371.
- ↑ 4.0 4.1 "Oxamniquine medical facts from Drugs.com". https://www.drugs.com/mtm/oxamniquine.html.
- ↑ "Drug Trials: Oxamniquine" (in en). Schistosomiasis: The St Lucia Project. CUP Archive. 1985. p. 298. ISBN 978-0-521-30312-5. https://books.google.com/books?id=XgE9AAAAIAAJ&pg=PA298.
- ↑ World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ↑ "Chapter 2: Bayer & E. Merck: Discovery and development of praziquantel*: Competing drugs for schistosomiasis treatment". International Strategies for Tropical Disease Treatments: Experiences with Praziquantel. EDM Research Series No. 026. WHO Essential Medicines. http://apps.who.int/medicinedocs/en/d/Jwhozip48e/6.4.html. Retrieved 10 December 2016.
- ↑ "Drugs for treating Schistosoma mansoni infection". The Cochrane Database of Systematic Reviews 2013 (2): CD000528. February 2013. doi:10.1002/14651858.CD000528.pub2. PMID 23450530.
- ↑ Martindale - The extra pharmacopoeia ; [evaluated information on the world's drugs and medicines] (31st ed.). London: Royal Pharmaceutical Society. 1996. p. 121. ISBN 978-0-85369-342-0.
External links
- "Oxamniquine". Drugs.com. https://www.drugs.com/MMX/Oxamniquine.html.
- "Schistosomiasis treatment". Institute of Tropical Medicine. Antwerp. http://www.itg.be/itg/DistanceLearning/LectureNotesVandenEndenE/40_Schistosomiasisp11.htm.
- "Oxamniquine". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/oxamniquine.
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