PYRANTEL

Physical properties

Pyrantel: MW 206. Embonate (also called pamoate): MW 595; pKa not known. Practically insoluble in water.
 

Pharmacology and mechanism of action

Pyrantel is a pyrimidine derivative with a broad spectrum anthelminthic activity. Its mechanism of action is similar to that of bephenium and levamisole (see under Levamisole).
 

Indications

Infections with Ascaris lumbricoides, Enterobius vermicularis, Ancylostoma duodenale and Necator americanus.
 

Side effects

Pyrantel is well tolerated in children and adults. Clinical studies carried out in several regions of the world have demonstrated mild and transient side effects. In a literature survey ^【1】of 1506 patients treated with 10 mg/kg of the drug, 299 subjects (20%) experienced side effects. The side effects were largely mild and transient. Frequent side effects were: nausea (4%), diarrhoea (4%), abdominal pain (4%), headache (3%) and vomiting (2%). Rare side effects included anorexia, fever, drowsiness, insomnia, skin rashes and elevation of serum aspartate aminotransferase (SGOT).
 

Contraindications and precautions

There are no known contraindications to the drug.
 

Interactions

Pyrantel antagonizes the effects of piperazine in vitro ^【2】, and potentiates the actions of levamisole in pigs ^【3】. The clinical significance of these interactions is as yet unknown.
 

Preparations

Available as pyrantel embonate: 725 mg embonate equals 250 mg base.
• Antiminth® (Pfizer). Oral suspension 50 mg base per ml.
• Combantrin® (Pfizer). Oral suspension 50 mg base per ml. Tablets (chewable) 250 mg base. Tablets (scored) 125, 250 mg base.
• Helmintox® (Innothera). Tablets 125, 250 mg base. Oral suspension 50 mg per ml.
 

References

1. Fossati C (1980). Sull’azione del pirantel-pamoato nella terapia delle infestationi da elminti. Clin Ter, 93, 713–717.
2. Terada M, Fujiu Y, Sano M (1983). Studies on chemotherapy of parasitic helminths (XVII). Effects of pyrantel on the motility of various parasitic helminths and isolated host tissues. Experientia, 39, 1020–1022.
3. Hsu W (1981). Drug interactions of levamisole with pyrantel tartrate and dichlorvos in pigs. Am J Vet Res, 42, 1912–1914.  

Uses

Pyrantel is a highly effective antihelmintic drug for enterobiasis, ascardiasis, ankylostomiasis, and necatoriasis. The antihelmintic effect is exhibited in the form of a powerful cholinomimetic effect on muscle cells of nematodes by binding with their cholinergic receptors, which leads to inhibition of neuromuscular transmission in the parasite, contraction of their musculature, and as a result, in the removal of the helminthes from the gastrointestinal tract of the host. It heals 85–100% of cases of ascariasis, and 90–100% of cases of enterobiasis. It is the drug of choice for Enterobius vermicularis, Acaris lumbricoides, as well as Ancylostoma duodenale, and Necator americanus. Synonyms of this drug are helmex, combantrin, antiminth, and others.

Pharmaceutical Applications

A tetrahydropyrimidine, formulated as the pamoate (embonate) in a 1:1 ratio and available as a suspension for oral administration. It is practically insoluble in water, but soluble in dimethyl sulfoxide. It is stable at room temperature.

Pharmacokinetics

By synthetic design most of the dose is passed unchanged in the feces. The portion that is absorbed (<5%) is metabolized and excreted in the urine.

Clinical Use

Ascariasis
Pinworm
Hookworm (especially A. duodenale)
Trichostrongyliasis
Higher and more prolonged doses may be necessary in hookworm infection caused by N. americanus. Pyrantel has been used in combination with an analog (oxantel) where concurrent whipworm infection was likely.

Side effects

Pyrantel should not be used at the same time as piperazine as their modes of action are antagonistic. Gastrointestinal upsets and, rarely, very mild neurological symptoms occur.

Synthesis

Pyrantel, 1,4,5,6-tetrahydro-1-methyl-2-[trans-2-(2-thienyl)vinyl]-pyrimidine (38.1.22), a derivative of tetrahydropyrimidine, is made from 3-(2-thienyl)-acrylonitrile (38.1.19), which is made in a Knoevangel condensation of furfural with cyanoacetic acid. Acidic hydrolysis of this makes 3-2(-thienyl)acrylamide (38.1.20). Reacting this with propansulfone gives an iminoester (38.1.21), which when reacted with N-methyltrimethylenediamine gives the desired pyrantel.

Raw materials

Preparation Products