Oxamniquine

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]

Oxamniquine
Clinical data
Trade namesVansil
AHFS/Drugs.comMicromedex Detailed Consumer Information
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • US: Not commercially available
Pharmacokinetic data
BioavailabilityReadily absorbed when taken by mouth
Metabolismliver
Elimination half-life1 to 2.5h
Excretionmainly in urine
Identifiers
  • (RS)-1,2,3,4-Tetrahydro-2-isopropylaminomethyl-7-nitro-6-quinolylmethanol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.040.491
Chemical and physical data
FormulaC14H21N3O3
Molar mass279.3 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • CC(C)NCC1CCC2=CC(=C(C=C2N1)[N+](=O)[O-])CO
  • InChI=1S/C14H21N3O3/c1-9(2)15-7-12-4-3-10-5-11(8-18)14(17(19)20)6-13(10)16-12/h5-6,9,12,15-16,18H,3-4,7-8H2,1-2H3 checkY
  • Key:XCGYUJZMCCFSRP-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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.

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.[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.

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.

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).

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

(R)-isomer
(S)-isomer

References
  1. World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 94. hdl:10665/44053. ISBN 978-9-2415-4765-9.
  2. Fenwick 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. ISBN 978-0-12-381507-1. Archived from the original on 2016-12-20.
  3. Kuhlmann FM, Fleckenstein JM (2016). "Antiparasitic Agents". In Cohen J, Powderly WG, Opal SM (eds.). Infectious Diseases (4th ed.). Elsevier Health Sciences. p. 1371. ISBN 978-0-7020-6338-1. Archived from the original on 2016-12-20.
  4. "Oxamniquine medical facts from Drugs.com". www.drugs.com. Archived from the original on 20 December 2016. Retrieved 10 December 2016.
  5. Jordan P (1985). "Drug Trials: Oxamniquine". Schistosomiasis: The St Lucia Project. CUP Archive. p. 298. ISBN 978-0-521-30312-5. Archived from the original on 2017-09-10.
  6. 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.
  7. "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 from the original on 20 December 2016. Retrieved 10 December 2016.
  8. 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. PMC 6532716. PMID 23450530.
  9. 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.
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