Oxamniquine
Encyclopedia
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.
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).
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.
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.
. According to one systematic review, it is equally effective as praziquantel
for treating S. mansoni
infections.
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.
Anthelmintic
Anthelmintics or antihelminthics are drugs that expel parasitic worms from the body, by either stunning or killing them. They may also be called vermifuges or vermicides .-Pharmaceutical classes:...
with schistosomicidal
Schistosoma
A genus of trematodes, Schistosoma, commonly known as blood-flukes and bilharzia, includes flatworms which are responsible for a highly significant parasitic infection of humans by causing the disease schistosomiasis, and are considered by the World Health Organization as the second most...
activity against Schistosoma mansoni
Schistosoma mansoni
Schistosoma mansoni is a significant parasite of humans, a trematode that is one of the major agents of the disease schistosomiasis. The schistosomiasis caused by Schistosoma mansoni is intestinal schistosomiasis....
, 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
Mesentery
In anatomy, the mesentery is the double layer of peritoneum that suspends the jejunum and ileum from the posterior wall of the abdomen. Its meaning, however, is frequently extended to include double layers of peritoneum connecting various components of the abdominal cavity.-Mesentery :The...
veins to the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, where the male worms are retained; the female worms return to the mesentery, but can no longer release eggs.
History
Oxamniquine was first described by Kaye and Woolhouse in 1972 as a metaboliteMetabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
of the compound UK 3883 (2-isopropylaminomethyl-6-methyl-7-nitro-1,2,3,4-tetrahydroquinoline). Initially, it was prepared by microbiological hydroxylation
Hydroxylation
Hydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...
in the presence of the fungus Aspergillus sclerotiorum. In 1979, Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
at Sandwich
Sandwich, Kent
Sandwich is a historic town and civil parish on the River Stour in the Non-metropolitan district of Dover, within the ceremonial county of Kent, south-east England. It has a population of 6,800....
was presented with the Queen's Award for Technological Achievement
Queen's Awards for Enterprise
The Queen's Awards for Enterprise is an awards programme for British businesses and other organizations who excel at international trade, innovation or sustainable development. They are the highest official UK awards for British businesses...
in recognition of the outstanding contribution made to tropical medicine by MANSIL (oxamniquine).
Pharmacokinetics
Peak plasmaBlood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
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 DNADNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
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
Praziquantel
Praziquantel is an anthelmintic effective against flatworms. Praziquantel is not licensed for use in humans in the UK; it is, however, available as a veterinary anthelmintic, and is available for use in humans on a named-patient basis....
, 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 schistosomiasisSchistosomiasis
Schistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...
. According to one systematic review, it is equally effective as praziquantel
Praziquantel
Praziquantel is an anthelmintic effective against flatworms. Praziquantel is not licensed for use in humans in the UK; it is, however, available as a veterinary anthelmintic, and is available for use in humans on a named-patient basis....
for treating S. mansoni
Schistosoma
A genus of trematodes, Schistosoma, commonly known as blood-flukes and bilharzia, includes flatworms which are responsible for a highly significant parasitic infection of humans by causing the disease schistosomiasis, and are considered by the World Health Organization as the second most...
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.
Brand names
- Vansil; (Pfizer) 250 mg capsules, syrup 250 mg/5 mL
- Mansil; 250 mg Tablets