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Identification
NamePiperazine
Accession NumberDB00592  (APRD00225)
Typesmall molecule
Groupsapproved
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
SynonymLanguageCode
PiperazidineNot AvailableNot Available
PiperazinGermanNot Available
Salts
Name/CAS Structure Properties
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
Brand names
NameCompany
AnteparNot Available
UvilonNot Available
VermidolNot Available
VermizineNot Available
Brand mixturesNot Available
Categories
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
Mass Specshow(8 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassDiazinanes
SubclassNot Available
Direct parentDiazinanes
Alternative parentsPiperazines; Polyamines; Dialkylamines
Substituentspolyamine; secondary aliphatic amine; secondary amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the diazinanes. These are organic compounds containing diazinane, a six-membered saturated heterocycle containing four carbon atoms and two nitrogen atoms.
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.
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
    N-mononitrosopiperazineDetails
    Piperazine
      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
      Property Value Probability
      Human Intestinal Absorption + 0.7652
      Blood Brain Barrier + 0.8549
      Caco-2 permeable + 0.6029
      P-glycoprotein substrate Substrate 0.7537
      P-glycoprotein inhibitor I Non-inhibitor 0.9851
      P-glycoprotein inhibitor II Non-inhibitor 0.996
      Renal organic cation transporter Non-inhibitor 0.562
      CYP450 2C9 substrate Non-substrate 0.9243
      CYP450 2D6 substrate Non-substrate 0.5478
      CYP450 3A4 substrate Non-substrate 0.8425
      CYP450 1A2 substrate Non-inhibitor 0.9165
      CYP450 2C9 substrate Non-inhibitor 0.9681
      CYP450 2D6 substrate Non-inhibitor 0.9632
      CYP450 2C19 substrate Non-inhibitor 0.9805
      CYP450 3A4 substrate Non-inhibitor 0.9928
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.99
      Ames test Non AMES toxic 0.9132
      Carcinogenicity Non-carcinogens 0.9171
      Biodegradation Not ready biodegradable 0.9436
      Rat acute toxicity 1.6247 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.5571
      hERG inhibition (predictor II) Non-inhibitor 0.7868
      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
      LiquidOral
      Solution / dropsOral
      SyrupOral
      Prices
      Unit descriptionCostUnit
      Desipramine HCl 150 mg tablet4.67USDtablet
      Desipramine HCl 100 mg tablet2.81USDtablet
      Desipramine HCl 75 mg tablet2.63USDtablet
      Desipramine HCl 50 mg tablet1.64USDtablet
      Desipramine HCl 10 mg tablet0.87USDtablet
      Desipramine HCl 25 mg tablet0.83USDtablet
      Piperazine citrate crystals0.05USDg
      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 solubility3.71e+02 g/lALOGPS
      logP-1.2ALOGPS
      logP-0.73ChemAxon
      logS0.63ALOGPS
      pKa (strongest basic)9.56ChemAxon
      physiological charge1ChemAxon
      hydrogen acceptor count2ChemAxon
      hydrogen donor count2ChemAxon
      polar surface area24.06ChemAxon
      rotatable bond count0ChemAxon
      refractivity25.45ChemAxon
      polarizability9.97ChemAxon
      number of rings1ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterNoChemAxon
      Veber's ruleYesChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      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 ReferenceNot Available
      External Links
      ResourceLink
      KEGG DrugD00807
      KEGG CompoundC07973
      PubChem Compound4837
      PubChem Substance46507642
      ChemSpider13835459
      ChEBI28568
      ChEMBLCHEMBL1412
      Therapeutic Targets DatabaseDAP001418
      PharmGKBPA450977
      HET169
      Drug Product Database97128
      Drugs.comhttp://www.drugs.com/cons/piperazine.html
      WikipediaPiperazine
      ATC CodesP02CB01R03DA09
      AHFS Codes
      • 08:08.00
      • 92:02.00*
      PDB EntriesNot Available
      FDA labelNot Available
      MSDSshow(71.9 KB)
      Interactions
      Drug InteractionsNot Available
      Food InteractionsNot Available

      1. Gamma-aminobutyric acid receptor subunit beta-3

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: agonist

      Components

      Name UniProt ID Details
      Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details

      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
      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
      3. Maskell PD, Wafford KA, Bermudez I: Effects of gamma-HCH and delta-HCH on human recombinant GABA receptors: dependence on GABA receptor subunit combination. Br J Pharmacol. 2001 Jan;132(1):205-12. Pubmed
      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

      1. Cytochrome P450 2D6

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 2D6 P10635 Details

      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. Epub 2009 Nov 24. Pubmed

      Comments
      Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11