Oxamniquine
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| Clinical data | |
|---|---|
| Trade names | Vansil |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| Routes of administration | By mouth |
| ATC code | |
| Pharmacokineticdata | |
| Bioavailability | Readily absorbed when taken by mouth |
| Metabolism | Liver |
| Eliminationhalf-life | 1 to 2.5h |
| Excretion | Kidney |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| PDB ligand | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.040.491 |
| Chemical and physical data | |
| Formula | C14H21N3O3 |
| Molar mass | 279.340g·mol−1 |
| 3D model (JSmol) | |
| Chirality | Racemic mixture |
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Oxamniquine,sold under the brand nameVansilamong others, is a medication used to treatschistosomiasisdue toSchistosoma mansoni.[1]Praziquantel,however, is often the preferred treatment.[2]It is givenby mouthand used as a single dose.[2]
Common side effects include sleepiness,headache,nausea,diarrhea,and reddish urine.[1]It is typically not recommended duringpregnancy,if possible.[1]Seizuresmay occur and therefore caution is recommended in people withepilepsy.[1]It works by causingparalysisof theparasitic worms.[3]It is in theanthelminticfamily of medications.[4]
Oxamniquine was first used medically in 1972.[5]It is on theWorld 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[edit]
Oxamniquine is used for treatment ofschistosomiasis.According to one systematic review,praziquantelis the standard treatment forS. mansoniinfections and oxamniquine also appears effective.[8]
Side effects[edit]
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[edit]
Peakplasmaconcentrations 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[edit]
It is ananthelminticwithschistosomicidalactivity againstSchistosoma mansoni,but not against otherSchistosomaspp. Oxamniquine is a potent single-dose agent for treatment ofS. mansoniinfection, and it causes worms to shift from themesentericveins to theliver,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 byDNAbinding, resulting in contraction and paralysis of the worms and eventual detachment from terminalvenulesin 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. Likepraziquantel,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[edit]
Oxamniquine was first described by Kaye and Woolhouse in 1972 as ametaboliteof the compound UK 3883 (2-isopropylaminomethyl-6-methyl-7-nitro-1,2,3,4-tetrahydroquinoline). Initially, it was prepared by enzymatichydroxylationvia the fungusAspergillus sclerotiorum.In 1979,PfizeratSandwichwas presented with theQueen's Award for Technological Achievementin recognition of the outstanding contribution made to tropical medicine by MANSIL (oxamniquine).[citation needed]
Brand names[edit]
- Vansil; (Pfizer) 250 mg capsules, syrup 250 mg/5 mL
- Mansil; 250 mg Tablets
Stereochemistry[edit]
Oxamniquine contains a stereocenter and consists of two enantiomers. This is aracemate,i.e. a 1: 1 mixture of (R) - and the (S) - form:
| Enantiomers of oxamniquine | |
|---|---|
 (R)-isomer |
 (S)-isomer |
References[edit]
- ^abcdeWorld Health Organization(2009). Stuart MC, Kouimtzi M, Hill SR (eds.).WHO Model Formulary 2008.World Health Organization. p. 94.hdl:10665/44053.ISBN978-9-2415-4765-9.
- ^abFenwick A, Utzinger J (2010)."Helminthic Diseases: Schistosomiasis".In Griffiths J, Maguire JH, Heggenhougen K, Quah SR (eds.).Public Health and Infectious Diseases.Elsevier. p. 351.ISBN978-0-12-381507-1.Archivedfrom the original on 20 December 2016.
- ^Kuhlmann FM, Fleckenstein JM (2016)."Antiparasitic Agents".In Cohen J, Powderly WG, Opal SM (eds.).Infectious Diseases(4th ed.). Elsevier Health Sciences. p. 1371.ISBN978-0-7020-6338-1.Archivedfrom the original on 20 December 2016.
- ^ab"Oxamniquine medical facts from Drugs.com".www.drugs.com.Archivedfrom the original on 20 December 2016.Retrieved10 December2016.
- ^Jordan P (1985)."Drug Trials: Oxamniquine".Schistosomiasis: The St Lucia Project.CUP Archive. p. 298.ISBN978-0-521-30312-5.Archivedfrom the original on 10 September 2017.
- ^World Health Organization(2019).World Health Organization model list of essential medicines: 21st list 2019.Geneva: World Health Organization.hdl:10665/325771.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. Archived fromthe originalon 20 December 2016.Retrieved10 December2016.
- ^Danso-Appiah A, Olliaro PL, Donegan S, Sinclair D, Utzinger J (February 2013)."Drugs for treating Schistosoma mansoni infection".The Cochrane Database of Systematic Reviews.2013(2): CD000528.doi:10.1002/14651858.CD000528.pub2.PMC6532716.PMID23450530.
- ^Martindale - The extra pharmacopoeia; [evaluated information on the world's drugs and medicines](31st ed.). London: Royal Pharmaceutical Society. 1996. p. 121.ISBN978-0-85369-342-0.
External links[edit]
- "Oxamniquine".Drugs.com.Archived fromthe originalon 5 March 2016.Retrieved23 January2018.
- "Schistosomiasis treatment".Institute of Tropical Medicine.Antwerp. Archived fromthe originalon 22 November 2004.
