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Identification
NamePiperazine
Accession NumberDB00592  (APRD00225)
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

Piperazine is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. Piperazine exists as small alkaline deliquescent crystals with a saline taste.

Piperazine was introduced to medicine as a solvent for uric acid. When taken into the body the drug is partly oxidized and partly eliminated unchanged. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful.

Piperazine was first introduced as an anthelmintic in 1953. A large number of piperazine compounds have anthelmintic action. Their mode of action is generally by paralysing parasites, which allows the host body to easily remove or expel the invading organism.

Structure
Thumb
Synonyms
Diethylenediamine
Piperazidine
Piperazin
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Versol 100mgliquid100 mgoralLes Produits Gerbex Inc.1970-12-311998-07-02Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Entacyl Granulespowder for solution2 goralShire Pharma Canada Ulc1995-12-312001-09-17Canada
Entacyl Granules 2.0gmpowder2 goralAllen & Hanburys A Glaxo Canada Ltd. Co.1951-12-311996-09-10Canada
Entacyl Susp 0.6gm/5mlsuspension600 mgoralAllen & Hanburys A Glaxo Canada Ltd. Co.1951-12-311998-07-29Canada
Entacyl Suspension-600mg/5mlsuspension600 mgoralRoberts Pharmaceutical Canada Inc.1997-04-012000-07-31Canada
Formule C34liquid100 mgoralHerbages Naturbec LtÉe.1979-12-31Not applicableCanada
Veriga 125liquid110 mgoralFrega Inc.1979-12-311996-09-09Canada
Vermirex Syrsyrup110 mgoralLes Laboratoires Vachon Inc.1968-12-312008-07-09Canada
Unapproved/Other Products Not Available
International Brands
NameCompany
AnteparNot Available
UvilonNot Available
VermidolNot Available
VermizineNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Piperazine adipate
ThumbNot applicableDBSALT001654
Piperazine citrate
Thumb
  • InChI Key: SWDXALWLRYIJHK-UHFFFAOYSA-N
  • Monoisotopic Mass: 278.11140094
  • Average Mass: 278.2591
DBSALT000775
Piperazine hexahydrate
Thumb
  • InChI Key: AVRVZRUEXIEGMP-UHFFFAOYSA-N
  • Monoisotopic Mass: 194.147786446
  • Average Mass: 194.2273
DBSALT000773
Piperazine hydrate
16832-43-2
Thumb
  • InChI Key: JRRBJSPQEVZLPI-UHFFFAOYSA-N
  • Monoisotopic Mass: 104.094963016
  • Average Mass: 104.1509
DBSALT000774
Piperazine hydrochloride
ThumbNot applicableDBSALT001623
Piperazine monohydrochloride
ThumbNot applicableDBSALT001632
Piperazine phosphate
ThumbNot applicableDBSALT001633
Piperazine sulfate
ThumbNot applicableDBSALT001655
Categories
UNII1RTM4PAL0V
CAS number110-85-0
WeightAverage: 86.1356
Monoisotopic: 86.08439833
Chemical FormulaC4H10N2
InChI KeyInChIKey=GLUUGHFHXGJENI-UHFFFAOYSA-N
InChI
InChI=1S/C4H10N2/c1-2-6-4-3-5-1/h5-6H,1-4H2
IUPAC Name
piperazine
SMILES
C1CNCCN1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as piperazines. These are compounds containing a piperazine ring, which is a saturated aliphatic six-member heterocyclic with two nitrogen atoms at positions 1 and 4, as well as four carbon atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazinanes
Sub ClassPiperazines
Direct ParentPiperazines
Alternative Parents
Substituents
  • Piperazine
  • Azacycle
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed as alternative treatment for ascariasis caused by Ascaris lumbricoides (roundworm) and enterobiasis (oxyuriasis) caused by Enterobius vermicularis (pinworm). It is also used to treat partial intestinal obstruction by the common roundworm, a condition primarily occurring in children.
PharmacodynamicsPiperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.
Mechanism of actionPiperazine is a GABA receptor agonist. Piperzine binds directly and selectively to muscle membrane GABA receptors, presumably causing hyperpolarization of nerve endings, resulting in flaccid paralysis of the worm. While the worm is paralyzed, it is dislodged from the intestinal lumen and expelled live from the body by normal intestinal peristalsis.
Related Articles
AbsorptionRapidly absorbed from the gastrointestinal tract
Volume of distributionNot Available
Protein binding60-70%
Metabolism

About 25% is metabolized in the liver. Piperazine is nitrosated to form N -mononitrosopiperazine (MNPz) in gastric juice, which is then metabolized to N-nitroso-3-hydroxypyrrolidine (NHPYR).

SubstrateEnzymesProduct
Piperazine
Not Available
N-mononitrosopiperazineDetails
Piperazine
Not Available
N-nitroso-3-hydroxypyrrolidineDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityLD50 = 5 g/kg (Human, oral). Symptoms of overdose include muscle fatigue, seizures, and difficulty breathing.
Affected organisms
  • Parasitic nematodes and other roundworms
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7652
Blood Brain Barrier+0.8549
Caco-2 permeable+0.6029
P-glycoprotein substrateSubstrate0.7537
P-glycoprotein inhibitor INon-inhibitor0.9851
P-glycoprotein inhibitor IINon-inhibitor0.996
Renal organic cation transporterNon-inhibitor0.562
CYP450 2C9 substrateNon-substrate0.9243
CYP450 2D6 substrateNon-substrate0.5478
CYP450 3A4 substrateNon-substrate0.8425
CYP450 1A2 substrateNon-inhibitor0.9165
CYP450 2C9 inhibitorNon-inhibitor0.9681
CYP450 2D6 inhibitorNon-inhibitor0.9632
CYP450 2C19 inhibitorNon-inhibitor0.9805
CYP450 3A4 inhibitorNon-inhibitor0.9928
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.99
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9171
BiodegradationNot ready biodegradable0.9436
Rat acute toxicity1.6247 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5571
hERG inhibition (predictor II)Non-inhibitor0.7868
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Schering corp sub schering plough corp
  • Glaxosmithkline
  • Sanofi aventis us llc
  • Bluline laboratories inc
  • Alpharma us pharmaceuticals division
  • Lannett co inc
  • Luitpold pharmaceuticals inc
  • Solvay pharmaceuticals
  • Impax laboratories inc
Packagers
  • Amend
Dosage forms
FormRouteStrength
Powder for solutionoral2 g
Powderoral2 g
Suspensionoral600 mg
Liquidoral100 mg
Liquidoral110 mg
Syruporal110 mg
Prices
Unit descriptionCostUnit
Desipramine HCl 150 mg tablet4.67USD tablet
Desipramine HCl 100 mg tablet2.81USD tablet
Desipramine HCl 75 mg tablet2.63USD tablet
Desipramine HCl 50 mg tablet1.64USD tablet
Desipramine HCl 10 mg tablet0.87USD tablet
Desipramine HCl 25 mg tablet0.83USD tablet
Piperazine citrate crystals0.05USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point106 °CPhysProp
boiling point146 °CPhysProp
water solubility1E+006 mg/L (at 25 °C)MERCK INDEX (1996)
logP-1.50HANSCH,C ET AL. (1995)
logS1.07ADME Research, USCD
pKa9.73PERRIN,DD (1972)
Predicted Properties
PropertyValueSource
Water Solubility371.0 mg/mLALOGPS
logP-1.2ALOGPS
logP-0.73ChemAxon
logS0.63ALOGPS
pKa (Strongest Basic)9.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area24.06 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity25.45 m3·mol-1ChemAxon
Polarizability9.97 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-9000000000-30cb9df5b98e3de11c25View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-9000000000-53fbd2cde978a20bcadfView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-b4c09986ae88107e9502View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-9000000000-d4c59a30517a103ac1a8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-9000000000-38be848b289304d565fbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000f-9000000000-bd7ae151b29cee31f3adView in MoNA
References
Synthesis Reference

Hong-Xin Li, Jose Guadalupe Santiesteban, Lenore Ann Emig, John Nelson Armor, “Triethylenediamine and piperazine synthesis using zeolite catalysts modified with a silicon-containing compound.” U.S. Patent US6084096, issued 0000.

US6084096
General ReferencesNot Available
External Links
ATC CodesP02CB01
AHFS Codes
  • 08:08.00
  • 92:02.00*
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (71.9 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Gaba-gated chloride ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRB3
Uniprot ID:
P28472
Molecular Weight:
54115.04 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Maskell PD, Wafford KA, Bermudez I: Effects of gamma-HCH and delta-HCH on human recombinant GABA(A) receptors: dependence on GABA(A) receptor subunit combination. Br J Pharmacol. 2001 Jan;132(1):205-12. [PubMed:11156579 ]
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23