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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
DiethylenediamineNot AvailableNot Available
PiperazidineNot AvailableNot Available
PiperazinGermanNot Available
PiperazineNot AvailableNot Available
Vermizine (tn)Not AvailableNot 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 KeyGLUUGHFHXGJENI-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
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
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 Solubility371.0ALOGPS
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 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

Targets

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

Enzymes

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

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