Oxamniquine

Oxamniquine
Systematic (IUPAC) name
(RS)-1,2,3,4-Tetrahydro-2-isopropylaminomethyl-7-nitro-6-quinolylmethanol
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
  • It is not known whether it will harm an unborn baby (FDA Pregnancy Category C)
  • Not commercially available in the United States
oral
Pharmacokinetic data
Bioavailability Readily absorbed after oral doses
Metabolism hepatic
Half-life 1 to 2.5h
Excretion mainly in urine
Identifiers
21738-42-1 Yes
P02BA02 QP52AA02
PubChem CID 4612
DrugBank DB01096 Yes
ChemSpider 4451 Yes
UNII 0O977R722D Yes
KEGG D00460 Yes
ChEBI CHEBI:7819 
ChEMBL CHEMBL847 Yes
PDB ligand ID OAQ (PDBe, RCSB PDB)
Chemical data
Formula C14H21N3O3
279.3
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Oxamniquine 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 in man, 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.[1]

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 microbiological hydroxylation in the presence of 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).

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.

Mode of action

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 to synthesis inhibition 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.

Uses

Oxamniquine is used for treatment of schistosomiasis. According to one systematic review, it is equally effective as praziquantel for treating S. mansoni infections.

Contraindications and precautions

Oxamniquine should not be taken during pregnancy.

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.

Dosage

Oral, 15 mg per kg of body weight two times a day for one day.

Brand names

References

  1. ↑ Martidale, The Extra Pharmacopoeia, 31st ed, p121

External links