Identification

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Name
Piperazine
Accession Number
DB00592  (APRD00225, DB11514)
Type
Small Molecule
Groups
Approved, Vet approved
Description

Piperazine is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. First used as a solvent for uric acid, the use of piperazine as an anthelmintic agent was first introduced in 1953. Upon entry into the systemic circulation, the drug is partly oxidized and partly eliminated as an unchanged compound. 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. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism.

Structure
Thumb
Synonyms
  • Diethylenediamine
  • Piperazidine
  • Piperazin
  • Piperazina
External IDs
FEMA NO. 4250 / P02CB01
Product Ingredients
IngredientUNIICASInChI Key
Piperazine adipateV7P5P122LB142-88-1BVEGEKOBSPXUJS-UHFFFAOYSA-N
Piperazine citrate63KP7FXF2I41372-10-5SWDXALWLRYIJHK-UHFFFAOYSA-N
Piperazine hexahydrateP3M07B8U64142-63-2AVRVZRUEXIEGMP-UHFFFAOYSA-N
Piperazine hydrate5O5QWX2S2D16832-43-2JRRBJSPQEVZLPI-UHFFFAOYSA-N
Piperazine hydrochloride17VU4Z4W88142-64-3CVVIJWRCGSYCMB-UHFFFAOYSA-N
Piperazine monohydrochloride7N36JHA4P67542-23-6MSQACBWWAIBWIC-UHFFFAOYSA-N
Piperazine phosphate8TIF7T48FP18534-18-4PMGABIJVFLPSLS-UHFFFAOYSA-N
Piperazine sulfateC8493J9B363597-26-0MYNIYCGOBKAQAO-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Versol 100mgLiquidOralLes Produits Gerbex Inc.1970-12-311998-07-02Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Entacyl GranulesPowder, for solutionOralShire Pharma Canada Ulc1995-12-312001-09-17Canada
Entacyl Granules 2.0gmPowderOralAllen & Hanburys A Glaxo Canada Ltd. Co.1951-12-311996-09-10Canada
Entacyl Susp 0.6gm/5mlSuspensionOralAllen & Hanburys A Glaxo Canada Ltd. Co.1951-12-311998-07-29Canada
Entacyl Suspension-600mg/5mlSuspensionOralRoberts Pharmaceutical1997-04-012000-07-31Canada
Formule C34LiquidOralHerbages Naturbec LtÉe.1979-12-31Not applicableCanada
Veriga 125LiquidOralFrega Inc.1979-12-311996-09-09Canada
Vermirex SyrSyrupOralLes Laboratoires Vachon Inc.1968-12-312008-07-09Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Antepar / Uvilon / Vermidol / Vermizine
Categories
UNII
1RTM4PAL0V
CAS number
110-85-0
Weight
Average: 86.1356
Monoisotopic: 86.08439833
Chemical Formula
C4H10N2
InChI Key
GLUUGHFHXGJENI-UHFFFAOYSA-N
InChI
InChI=1S/C4H10N2/c1-2-6-4-3-5-1/h5-6H,1-4H2
IUPAC Name
piperazine
SMILES
C1CNCCN1

Pharmacology

Indication

Used 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.

Pharmacodynamics

Piperazine 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 action

Piperazine 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.

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit beta-3
agonist
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Rapidly absorbed from the gastrointestinal tract

Volume of distribution
Not Available
Protein binding

60-70%

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).

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

LD50 = 5 g/kg (Human, oral). Symptoms of overdose include muscle fatigue, seizures, and difficulty breathing.

Affected organisms
  • Parasitic nematodes and other roundworms
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Piperazine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Piperazine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Piperazine.
5-methoxy-N,N-dimethyltryptamineThe metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Piperazine.
AbataceptThe metabolism of Piperazine can be increased when combined with Abatacept.
AbirateroneThe metabolism of Piperazine can be decreased when combined with Abiraterone.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Piperazine.
AcebutololThe metabolism of Piperazine can be decreased when combined with Acebutolol.
AcetaminophenThe metabolism of Piperazine can be decreased when combined with Acetaminophen.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Piperazine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take without regard to meals.

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 References
Not Available
External Links
Human Metabolome Database
HMDB0014730
KEGG Drug
D00807
KEGG Compound
C07973
PubChem Compound
4837
PubChem Substance
46507642
ChemSpider
13835459
ChEBI
28568
ChEMBL
CHEMBL1412
Therapeutic Targets Database
DAP001418
PharmGKB
PA450977
HET
PZE
Drugs.com
Drugs.com Drug Page
Wikipedia
Piperazine
ATC Codes
P02CB01 — Piperazine
AHFS Codes
  • 08:08.00 — Anthelmintics
PDB Entries
3qf1 / 5g4b / 6esm
MSDS
Download (71.9 KB)

Clinical Trials

Clinical Trials
Not Available

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 solutionOral
PowderOral
SuspensionOral
LiquidOral
SyrupOral
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)106 °CPhysProp
boiling point (°C)146 °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 FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Download (8 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-9000000000-30cb9df5b98e3de11c25
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-9000000000-53fbd2cde978a20bcadf
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-b4c09986ae88107e9502
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-9000000000-d4c59a30517a103ac1a8
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-9000000000-38be848b289304d565fb
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-000f-9000000000-bd7ae151b29cee31f3ad
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-9000000000-66908ddfe69d5ab2d477
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-9000000000-044d64bffabbb2fef60d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-e8dc1b97c0a6a42c758a
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-f2155d32a2f87a5d94d4
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-1d40ce3733d7fba748f0

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Piperazines
Alternative Parents
Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Piperazine / Azacycle / Secondary amine / Secondary aliphatic amine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Amine / Aliphatic heteromonocyclic compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
azacycloalkane, saturated organic heteromonocyclic parent, piperazines (CHEBI:28568)

Targets

Kind
Protein
Organism
Humans
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...
Gene Name
GABRB3
Uniprot ID
P28472
Uniprot Name
Gamma-aminobutyric acid receptor subunit beta-3
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
Humans
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Maurer HH, Kraemer T, Springer D, Staack RF: Chemistry, pharmacology, toxicology, and hepatic metabolism of designer drugs of the amphetamine (ecstasy), piperazine, and pyrrolidinophenone types: a synopsis. Ther Drug Monit. 2004 Apr;26(2):127-31. [PubMed:15228152]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2019 12:18