Identification

Name
Chlorcyclizine
Accession Number
DB08936
Type
Small Molecule
Groups
Approved
Description

Chlorcyclizine is a first generation phenylpiperazine class antihistamine used to treat urticaria, rhinitis, pruritus, and other allergy symptoms. Chlorcyclizine also has some local anesthetic, anticholinergic, and antiserotonergic properties, and can be used as an antiemetic.

Structure
Thumb
Synonyms
  • Chlorcyclizin
  • Chlorcyclizine
  • Chlorcyclizinum
  • Clorciclicina
  • Clorciclizina
  • Clorciclizinio
External IDs
Compound 47-282
Product Ingredients
IngredientUNIICASInChI Key
Chlorcyclizine hydrochlorideNPB7A7874U14362-31-3MSIJLVMSKDXAQN-UHFFFAOYSA-N
Active Moieties
NameKindUNIICASInChI Key
Chloride ionionicQ32ZN4869816887-00-6VEXZGXHMUGYJMC-UHFFFAOYSA-M
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AhistTablet25 mg/1OralMagna Pharmaceuticals2013-01-15Not applicableUs
Bonine KidsTablet, chewable25 mg/1OralInsight Pharmaceuticals2009-06-08Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
BicloraChlorcyclizine hydrochloride (12.5 mg/5mL) + Chlophedianol hydrochloride (12.5 mg/5mL)LiquidOralHawthorn Pharmaceuticals, Inc.2012-10-312014-10-23Us
BicloraChlorcyclizine hydrochloride (12.5 mg/5mL) + Chlophedianol hydrochloride (12.5 mg/5mL)LiquidOralPhysicians Total Care, Inc.2013-01-02Not applicableUs
BicloraChlorcyclizine hydrochloride (25 mg/1) + Chlophedianol hydrochloride (25 mg/1)TabletOralHawthorn Pharmaceuticals, Inc.2012-11-302014-10-23Us
biclora-DChlorcyclizine hydrochloride (25 mg/1) + Chlophedianol hydrochloride (25 mg/1) + Pseudoephedrine hydrochloride (60 mg/1)TabletOralHawthorn Pharmaceuticals, Inc.2012-11-302014-11-30Us
biclora-DChlorcyclizine hydrochloride (12.5 mg/5mL) + Chlophedianol hydrochloride (12.5 mg/5mL) + Pseudoephedrine hydrochloride (30 mg/5mL)LiquidOralHawthorn Pharmaceuticals, Inc.2012-10-082014-10-23Us
DallergyChlorcyclizine hydrochloride (12.5 mg/1) + Phenylephrine (5 mg/1)Tablet, chewableOralLaser Pharmaceuticals Llc2011-11-012011-11-25Us
DallergyChlorcyclizine hydrochloride (25 mg/1) + Phenylephrine hydrochloride (10 mg/1)TabletOralLaser Pharmaceuticals, LLC2011-11-012011-11-15Us
DallergyChlorcyclizine hydrochloride (12.5 mg/5mL) + Phenylephrine hydrochloride (5 mg/5mL)SyrupOralLaser Pharmaceuticals Llc2011-10-182017-07-03Us
NasopenChlorcyclizine hydrochloride (9.375 mg/5mL) + Pseudoephedrine hydrochloride (30 mg/5mL)LiquidOralGm Pharmaceuticals2011-06-062015-02-28Us
NasotussChlorcyclizine hydrochloride (25 mg/5mL) + Codeine phosphate hemihydrate (10 mg/5mL) + Phenylephrine hydrochloride (10 mg/5mL)LiquidOralHawthorn Pharmaceuticals, Inc.2010-11-082012-12-09Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Notuss-NXChlorcyclizine hydrochloride (9.375 mg/5mL) + Codeine phosphate hemihydrate (10 mg/5mL)LiquidOralSj Pharmaceuticals, Llc2010-11-032012-08-18Us
Notuss-NXDChlorcyclizine hydrochloride (9.375 mg/5mL) + Codeine phosphate hemihydrate (10 mg/5mL) + Pseudoephedrine hydrochloride (30 mg/5mL)LiquidOralSj Pharmaceuticals, Llc2010-11-032012-08-18Us
International/Other Brands
Di-Paralene / Mantadil / Pruresidine / Trihistan / Zimin (New Chemical)
Categories
UNII
M26C4IP44P
CAS number
82-93-9
Weight
Average: 300.826
Monoisotopic: 300.139326389
Chemical Formula
C18H21ClN2
InChI Key
WFNAKBGANONZEQ-UHFFFAOYSA-N
InChI
InChI=1S/C18H21ClN2/c1-20-11-13-21(14-12-20)18(15-5-3-2-4-6-15)16-7-9-17(19)10-8-16/h2-10,18H,11-14H2,1H3
IUPAC Name
1-[(4-chlorophenyl)(phenyl)methyl]-4-methylpiperazine
SMILES
CN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1

Pharmacology

Indication
Not Available
Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Readily absorbed after oral administration and widely distributed throughout the body. Metabolised by N-demethylation to form norchlorcyclizine and by N-oxidation.

Volume of distribution

After a single oral dose of 2 mg/kg to 4 subjects, average peak plasma concentrations of about 0.05 mg/L and 0.03 mg/L were attained in 5 h for unchanged drug and norchlorcyclizine, respectively. After oral administration of 50 mg 3 times a day for 6 days, plasma concentrations of norchlorcyclizine of 0.05 to 0.11 mg/L were reported on the first day after the cessation of treatment and plasma concentrations of 0.02 to 0.04 mg/L were found on the 10th day after cessation of treatment [Kuntzman et al. 1973].

Protein binding

about 85 to 90%.

Metabolism

High concentrations of the N-desmethyl metabolite are found in the liver, lungs, kidney, and spleen.

Route of elimination

Slowly excreted in the urine; measurable amounts of norchlorcyclizine have been detected in the urine for up to 3 weeks after the cessation of chronic oral administration. About 0.5% of a single dose is excreted in the urine as the N-oxide.

Half life

about 12 h.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Chlorcyclizine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Chlorcyclizine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Chlorcyclizine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Chlorcyclizine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Chlorcyclizine.
AbexinostatThe risk or severity of QTc prolongation can be increased when Chlorcyclizine is combined with Abexinostat.
AcebutololThe risk or severity of QTc prolongation can be increased when Chlorcyclizine is combined with Acebutolol.
AceprometazineThe risk or severity of QTc prolongation can be increased when Chlorcyclizine is combined with Aceprometazine.
AcetyldigoxinThe risk or severity of QTc prolongation can be increased when Chlorcyclizine is combined with Acetyldigoxin.
AcrivastineThe risk or severity of QTc prolongation can be increased when Chlorcyclizine is combined with Acrivastine.
AdenosineThe risk or severity of QTc prolongation can be increased when Chlorcyclizine is combined with Adenosine.
Food Interactions
Not Available

References

Synthesis Reference

Baltzly, R. and Castillo, J.C.; U.S. Patent 2,630,435; March 3, 1953; assigned to Burroughs- Wellcome & Co. (USA.) Inc.

General References
  1. Enright BP, Gu YZ, Snyder RD, Dugyala RR, Obert LA, Treinen KA, McIntyre BS, Veneziale RW: Effects of the histamine H1 antagonist chlorcyclizine on rat fetal palate development. Birth Defects Res B Dev Reprod Toxicol. 2010 Dec;89(6):474-84. doi: 10.1002/bdrb.20261. [PubMed:21058326]
  2. KUNTZMAN R, KLUTCH A, TSAI I, BURNS JJ: PHYSIOLOGICAL DISTRIBUTION AND METABOLIC INACTIVATION OF CHLORCYCLIZINE AND CYCLIZINE. J Pharmacol Exp Ther. 1965 Jul;149:29-35. [PubMed:14334288]
External Links
Human Metabolome Database
HMDB0240224
PubChem Compound
2710
PubChem Substance
175427165
ChemSpider
2609
BindingDB
50329371
ChEBI
94402
ChEMBL
CHEMBL22150
Drugs.com
Drugs.com Drug Page
Wikipedia
Chlorcyclizine
ATC Codes
R06AE04 — Chlorcyclizine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral25 mg/1
TabletOral
Tablet, chewableOral25 mg/1
SyrupOral
Tablet, chewableOral
LiquidOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)216Baltzly, R. and Castillo, J.C.; U.S. Patent 2,630,435; March 3, 1953; assigned to Burroughs- Wellcome & Co. (USA.) Inc.
Predicted Properties
PropertyValueSource
Water Solubility0.0424 mg/mLALOGPS
logP4.16ALOGPS
logP4.15ChemAxon
logS-3.8ALOGPS
pKa (Strongest Basic)7.63ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity89.74 m3·mol-1ChemAxon
Polarizability33.89 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Download (22.7 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-006t-9261000000-d789fa33e2113c522133
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
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0090000000-b26de1d44bba1bbba71d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0090000000-cd86d2a7b60fba9a8093
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0490000000-d2ef728df7bda2d67974
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0920000000-6337d2bca22bf828e822
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-cb2916a03edaa19b1b71
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-26236f7b47a790c10e10
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-3c7d8992d76da5c7bd63
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-a5c6cf14866d0a23a877
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-02t9-2900000000-5462dc3ded9a8297443e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0090000000-c4ac9541a144f323398e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0uxr-0590000000-ce9f2e2451aeb092dd88
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0920000000-587c135265c1fbd939db
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-2788ec685444238cbb77
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-300ed2322e3d24ba24cd
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0009000000-6b6c6de087e1c9ad671e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udl-1192000000-2e1124f2124d4e765271
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udl-1290000000-cf510eabf20fd368c6d6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0gdi-2890000000-77c12238ddf4cb2c7502
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-1930000000-89c336a1c9b2a2f0a9b7
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-1910000000-e63b88c0cac40a117f1d

Taxonomy

Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
N-methylpiperazines / Chlorobenzenes / Aralkylamines / Aryl chlorides / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Diphenylmethane / Chlorobenzene / Halobenzene / N-methylpiperazine / Aralkylamine / N-alkylpiperazine / Aryl chloride / Aryl halide / 1,4-diazinane / Piperazine
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Enright BP, Gu YZ, Snyder RD, Dugyala RR, Obert LA, Treinen KA, McIntyre BS, Veneziale RW: Effects of the histamine H1 antagonist chlorcyclizine on rat fetal palate development. Birth Defects Res B Dev Reprod Toxicol. 2010 Dec;89(6):474-84. doi: 10.1002/bdrb.20261. [PubMed:21058326]

Drug created on January 28, 2014 13:53 / Updated on November 06, 2018 13:13