Identification

Name
Pyrantel
Accession Number
DB11156
Type
Small Molecule
Groups
Approved, Vet approved
Description

Pyrantel is a pyrimidine-derivative anthelmintic agent for the oral treatment of various parasitic worm infections including ascariasis, hookworm infections, enterobiasis (pinworm infection), trichostrongyliasis, and trichinellosis [17].

Pyrantel was initially described in 1965 by researchers from Pfizer who sought cyclic amidines with suitable pharmacokinetic properties (specifically, duration of action) for use as an anthelmintic drug. Pyrantel is mainly available in formulations for dogs and cats as the embonate salt, containing a 34.7% pyrantel base [14].

Pyrantel is on the World Health Organization's List of Essential Medicines, which are the safest and most effective medicines required in a functioning health system [15], [16].

A depolarizing neuromuscular-blocking agent causing longstanding nicotinic receptor activation, resulting in spastic paralysis of susceptible nematodes (worms). Pyrantel has shown to be effective after a single dose [18].

In humans, it is administered as pyrantel pamoate [3],[4],[8],[12].

Structure
Thumb
Synonyms
  • pirantel
  • pyrantel
  • Pyrantelum
Product Ingredients
IngredientUNIICASInChI Key
Pyrantel citrate1YXE665Z2S5685-86-9YJGGCARNRYGSPA-IPZCTEOASA-N
Pyrantel pamoate81BK194Z5M22204-24-6AQXXZDYPVDOQEE-MXDQRGINSA-N
Pyrantel tartrateSC82VF048033401-94-4VWRCYAZJKNPEQR-NIEARKAZSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Jaa Pyral 35 Tablet 35mgTablet35 mgOralJaapharm Canada Inc.1989-12-31Not applicableCanada
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Combantrin Oral Suspension 50mg/mlSuspension50 mgOralMcneil Consumer Healthcare Division Of Johnson & Johnson Inc1973-12-31Not applicableCanada
Combantrin Tab 125mgTablet125 mgOralMcneil Consumer Healthcare Division Of Johnson & Johnson Inc1973-12-31Not applicableCanada
CVS Pinworm TreatmentSuspension144 mg/1mLOralCVS Health2016-12-15Not applicableUs
Jaa Pyral 125 Tablet 125mgTablet125 mgOralJaapharm Canada Inc.1998-11-27Not applicableCanada
Jaa Pyral P Oral Paste - 125mg/gPaste125 mgOralJaapharm Canada Inc.1995-12-31Not applicableCanada
Jaa Pyral S Suspension 50mg/76Suspension50 mgOralJaapharm Canada Inc.1995-12-31Not applicableCanada
Jamp-pyrantel PamoateTablet125 mgOralJamp Pharma Corporation2013-12-13Not applicableCanada
Jamp-pyrantel Pamoate SuspensionSuspension50 mgOralJamp Pharma Corporation2014-03-25Not applicableCanada
ParasitexxSuspension144 mg/1mLOralDannso corp./d.b.a. Essential Products2017-05-01Not applicableUs
ParasitolSuspension144 mg/1mLOralMenper Distributors2013-01-01Not applicableUs
Categories
UNII
4QIH0N49E7
CAS number
15686-83-6
Weight
Average: 206.31
Monoisotopic: 206.087769633
Chemical Formula
C11H14N2S
InChI Key
YSAUAVHXTIETRK-AATRIKPKSA-N
InChI
InChI=1S/C11H14N2S/c1-13-8-3-7-12-11(13)6-5-10-4-2-9-14-10/h2,4-6,9H,3,7-8H2,1H3/b6-5+
IUPAC Name
1-methyl-2-[(E)-2-(thiophen-2-yl)ethenyl]-1,4,5,6-tetrahydropyrimidine
SMILES
[H]\C(=C(\[H])C1=NCCCN1C)C1=CC=CS1

Pharmacology

Indication

For the treatment of enterobiasis including roundworm (ascariasis), pinworm (enterobius) and hookworm (strongyloides) and hookworm (ancylostoma) in the pyrantel pamoate form [8].

Pyrantel is available in various formulations for humans, dogs, and cats as the pamoate (US Pharmacopeia nomenclature) or embonate (European Pharmacopoeia nomenclature) salt, which contains 34.7% pyrantel base combined with pamoic acid [8]. [14], [4].

Pyrantel pamoate (embonate) ingested orally is effective for removal and control of ascarid and hookworm infections in puppies and dogs (adult Toxocara canis, Toxascaris leonina, Ancylostoma tubaeforme, An. braziliense, Uncinaria stenocephala), cats (adult Toxocara cati, Toxa. leonina, An. caninum, An. braziliense, U. stenocephala), horses and ponies (adult and immature Parascaris equorum, adult Strongylus vulgaris, S. edentatus, S. equinus, Cyathostomes (Triodontophorus spp., Cyathostomum spp., Cylicodontophorus spp., Cylicocyclus spp., Cylicostephanus spp., Poteriostomum spp.), Oxyuris equi, Anoplocephala perfoliata), swine (adult Ascaris suum, Oesophagostomum dentatum), and humans (adult A. lumbricoides, Enterobius vermicularis, An. duodenale, Necator americanus) [14].

Pharmacodynamics

It has similar properties to both competitive and depolarizing neuromuscular blocking agents, which leads to the understanding of the paralytic effect of the drug has on parasites, ultimately resulting in the death of the parasite [16], [8].

Mechanism of action

By promoting the release of acetylcholine, inhibiting cholinesterase, and stimulating ganglionic neurons, pyrantel serves as a depolarizing neuromuscular blocking agent in helminths. This causes extensive depolarization of the helminth muscle membrane, resulting in tension to the helminth's muscles, leading to paralysis and release of their attachment to the host organism intestinal walls [8].

This action is unlike piperazine, which is a hyperpolarizing neuromuscular blocking agent that causes relaxation of the helminth muscles, leading to a subsequent detachment from the intestinal wall. Excretion of the parasites in the feces occurs by normal peristalsis [7].

TargetActionsOrganism
UG-protein coupled receptor 35Not AvailableHuman
NMuscarinic acetylcholine receptor M1
antagonist
agonist
Human
Absorption

Pyrantel is poorly absorbed from the GI tract of humans [8], [21].

Peak serum concentrations occur 1–3 hours after a single dose [17].

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Pyrantel is administered orally. The poor solubility of the pamoate salt offers the advantage of reduced absorption from the gastrointestinal tract and allows the drug to reach and act against parasites in the large intestine. Metabolism of pyrantel is rapid [22]. The absorbed drug is partly metabolized in the liver [20].

Route of elimination

Approximately 50% of an oral dose is excreted unchanged in feces; 7% excreted in urine as unchanged drug and metabolites [17].

Half life

In pigs, following intravenous administration, pyrantel exhibited a half-life of 1.75 +/- 0.19 h [5].

Clearance
Not Available
Toxicity

Mild adverse effects include nausea, vomiting, diarrhea, headache, and dizziness [8].

LD50 in rats is 535 mg/kg [10].

Reported effects in humans in case of overdose include gastrointestinal disturbance, central nervous system effects, and superficial skin reactions. In one study, serum aspartate aminotransferase (AST) and serum alanine-aminotransferase (ALT) values were increased in approximately 2% of patients [19].

Pyrantel should be used with caution in patients with severe malnutrition or anemia. Supportive therapy is recommended for anemic, dehydrated, or malnourished patients before administration of the drug [12].

Pyrantel pamoate has been placed in pregnancy category C. This refers to the fact that animal studies have revealed adverse effects on the fetus (teratogenic/embryocidal, or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus [9].Data on the use of pyrantel pamoate in pregnant women are quite limited. In mass treatment programs for which the World Health Organization (WHO) has observed that the benefits of treatment outweigh the risks, WHO allows the use of pyrantel pamoate in the 2nd and 3rd trimesters of pregnancy, due to the fact that the effects of pyrantel on birth outcome are uncertain. The risk of treatment in pregnant women already known to have an infection needs to be balanced with the risk of disease progression if treatment were to be omitted [9]. Individuals with liver disease are more susceptible to the toxicity in cases of pyrantel overexposure [9], [11].

There are no data regarding the presence of pyrantel in breast milk. Pyrantel is poorly absorbed from the GI tract; therefore, excretion into breast milk may be minimal. Some experts recommend that a single dose of pyrantel therapy may be given to breastfeeding women [8].

Affected organisms
  • Humans
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Pyrantel is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Pyrantel.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Pyrantel.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Pyrantel.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Pyrantel is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Pyrantel.
AbacavirAbacavir may decrease the excretion rate of Pyrantel which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Pyrantel which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Pyrantel which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Pyrantel which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Aubry ML, Cowell P, Davey MJ, Shevde S: Aspects of the pharmacology of a new anthelmintic: pyrantel. Br J Pharmacol. 1970 Feb;38(2):332-44. [PubMed:5417856]
  2. Rayes D, De Rosa MJ, Spitzmaul G, Bouzat C: The anthelmintic pyrantel acts as a low efficacious agonist and an open-channel blocker of mammalian acetylcholine receptors. Neuropharmacology. 2001 Aug;41(2):238-45. [PubMed:11489460]
  3. Gokbulut C, Aksit D, Smaldone G, Mariani U, Veneziano V: Plasma pharmacokinetics, faecal excretion and efficacy of pyrantel pamoate paste and granule formulations following per os administration in donkeys naturally infected with intestinal strongylidae. Vet Parasitol. 2014 Sep 15;205(1-2):186-92. doi: 10.1016/j.vetpar.2014.06.026. Epub 2014 Jun 26. [PubMed:25015542]
  4. Fasanmade AA, Akanni AO, Olaniyi AA, Fasanmade AA, Tayo F: Bioequivalence of pyrantel pamoate dosage forms in healthy human subjects. Biopharm Drug Dispos. 1994 Aug;15(6):527-34. [PubMed:7993990]
  5. Bjorn H, Hennessy DR, Friis C: The kinetic disposition of pyrantel citrate and pamoate and their efficacy against pyrantel-resistant Oesophagostomum dentatum in pigs. Int J Parasitol. 1996 Dec;26(12):1375-80. [PubMed:9024887]
  6. Li XQ, Bjorkman A, Andersson TB, Gustafsson LL, Masimirembwa CM: Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42. Epub 2003 Aug 12. [PubMed:12920490]
  7. Pharmacokinetics of praziquantel and pyrantel pamoate combination following oral administration in cats [Link]
  8. Pyrantel Pamoate PDR [Link]
  9. CDC for healthcare professionals [Link]
  10. MSDS for pyrantel [Link]
  11. Strongidpaste [Link]
  12. Pyrantel Dosage [Link]
  13. Pyrantel Pamoate [Link]
  14. Pyrantel, Science Direct [Link]
  15. Pediatric Ascaris Medication [Link]
  16. Summary of product characteristics [Link]
  17. Pyrantel Pamoate Monograph [Link]
  18. Pyrantel MeSH NIH [Link]
  19. Principles and Practice of Infectious Diseases [Link]
  20. Pharmacotherapeutics For Advanced Practice Nurse Prescribers [Link]
  21. Delmar Nurse's Drug Handbook 2012 Edition [Link]
  22. MSD vet manual [Link]
External Links
KEGG Drug
D08451
KEGG Compound
C07409
PubChem Compound
708857
PubChem Substance
347827925
ChemSpider
618121
ChEBI
8654
ChEMBL
CHEMBL1626223
Wikipedia
Pyrantel
ATC Codes
P02CC01 — Pyrantel
AHFS Codes
  • 08:08.00 — Anthelmintics
MSDS
Download (41.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentHookworm Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral125 mg
TabletOral35 mg
PasteOral125 mg
SuspensionOral50 mg
Tablet, chewableOral250 mg/1
SuspensionOral144 mg/1mL
LiquidOral5 mL/250mL
SuspensionOral5 g/100mL
SuspensionOral50 mg/1mL
TabletOral180 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityinsoluble in waterMSDS
Predicted Properties
PropertyValueSource
Water Solubility0.118 mg/mLALOGPS
logP2.69ALOGPS
logP1.96ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)10.71ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area15.6 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity61.81 m3·mol-1ChemAxon
Polarizability23.32 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as hydropyrimidines. These are compounds containing a hydrogenated pyrimidine ring (i.e. containing less than the maximum number of double bonds.).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Hydropyrimidines
Alternative Parents
Imidolactams / Thiophenes / Heteroaromatic compounds / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Carboxamidines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Hydropyrimidine / 1,4,5,6-tetrahydropyrimidine / Imidolactam / Thiophene / Heteroaromatic compound / Organic 1,3-dipolar compound / Propargyl-type 1,3-dipolar organic compound / Carboximidamide / Amidine / Carboxylic acid amidine
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
carboxamidine, thiophenes, 1,4,5,6-tetrahydropyrimidines (CHEBI:8654)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
G-protein coupled receptor activity
Specific Function
Acts as a receptor for kynurenic acid, an intermediate in the tryptophan metabolic pathway. The activity of this receptor is mediated by G-proteins that elicit calcium mobilization and inositol pho...
Gene Name
GPR35
Uniprot ID
Q9HC97
Uniprot Name
G-protein coupled receptor 35
Molecular Weight
34071.89 Da
References
  1. Zhao P, Sharir H, Kapur A, Cowan A, Geller EB, Adler MW, Seltzman HH, Reggio PH, Heynen-Genel S, Sauer M, Chung TD, Bai Y, Chen W, Caron MG, Barak LS, Abood ME: Targeting of the orphan receptor GPR35 by pamoic acid: a potent activator of extracellular signal-regulated kinase and beta-arrestin2 with antinociceptive activity. Mol Pharmacol. 2010 Oct;78(4):560-8. doi: 10.1124/mol.110.066746. Epub 2010 Jul 22. [PubMed:20826425]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Antagonist
Agonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Rayes D, De Rosa MJ, Spitzmaul G, Bouzat C: The anthelmintic pyrantel acts as a low efficacious agonist and an open-channel blocker of mammalian acetylcholine receptors. Neuropharmacology. 2001 Aug;41(2):238-45. [PubMed:11489460]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Leukotriene-b4 20-monooxygenase activity
Specific Function
Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity toward prostaglandins A1 and E1. Oxidizes arachidonic acid to 2...
Gene Name
CYP4A11
Uniprot ID
Q02928
Uniprot Name
Cytochrome P450 4A11
Molecular Weight
59347.31 Da
References
  1. Li XQ, Bjorkman A, Andersson TB, Gustafsson LL, Masimirembwa CM: Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42. Epub 2003 Aug 12. [PubMed:12920490]

Drug created on December 03, 2015 09:51 / Updated on November 18, 2018 13:31