Identification

Name
Cyclizine
Accession Number
DB01176  (APRD00061)
Type
Small Molecule
Groups
Approved
Description

A histamine H1 antagonist given by mouth or parenterally for the control of postoperative and drug-induced vomiting and in motion sickness. (From Martindale, The Extra Pharmacopoeia, 30th ed, p935)

Structure
Thumb
Synonyms
  • (+-)-1-Diphenylmethyl-4-methylpiperazine
  • (±)-1-diphenylmethyl-4-methylpiperazine
  • (N-Benzhydryl)(n'-methyl)diethylenediamine
  • 1-(Diphenylmethyl)-4-methylpiperazine
  • 1-Benzhydryl-4-methylpiperazin
  • Ciclizina
  • Cyclizine
  • Cyclizinum
  • N-Benzhydryl-N'-methylpiperazine
  • N-methyl-N'-benzhydrylpiperazine
Product Ingredients
IngredientUNIICASInChI Key
Cyclizine hydrochlorideW0O1NHP4WE303-25-3UKPBEPCQTDRZSE-UHFFFAOYSA-N
Cyclizine lactate861R00J9865897-19-8JOROEVAWQLGPFQ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Marzine Inj 50mg/mlLiquid50 mgIntramuscular; IntravenousGlaxo Wellcome1988-12-311998-07-30Canada
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CyclivertTablet25 mg/25mgOralLaser Pharmaceuticals Llc2011-11-012017-07-03Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Megral TabsCyclizine hydrochloride (50 mg) + Caffeine (100 mg) + Ergotamine tartrate (2 mg)TabletOralGlaxo Wellcome1989-12-312001-03-01Canada
International/Other Brands
Emoquil / Marezine / Marzine (GlaxoSmithKline) / Valoid (GlaxoSmithKline)
Categories
UNII
QRW9FCR9P2
CAS number
82-92-8
Weight
Average: 266.3807
Monoisotopic: 266.178298714
Chemical Formula
C18H22N2
InChI Key
UVKZSORBKUEBAZ-UHFFFAOYSA-N
InChI
InChI=1S/C18H22N2/c1-19-12-14-20(15-13-19)18(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18H,12-15H2,1H3
IUPAC Name
1-(diphenylmethyl)-4-methylpiperazine
SMILES
CN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1

Pharmacology

Indication

For prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness, and vertigo (dizziness caused by other medical problems).

Associated Conditions
Pharmacodynamics

Cyclizine is a piperazine-derivative antihistamine used as an antivertigo/antiemetic agent. Cyclizine is used in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Although the mechanism by which cyclizine exerts its antiemetic and antivertigo effects has not been fully elucidated, its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone. It also possesses anticholinergic, antihistaminic, central nervous system depressant, and local anesthetic effects.

Mechanism of action

Vomiting (emesis) is essentially a protective mechanism for removing irritant or otherwise harmful substances from the upper GI tract. Emesis or vomiting is controlled by the vomiting centre in the medulla region of the brain, an important part of which is the chemotrigger zone (CTZ). The vomiting centre possesses neurons which are rich in muscarinic cholinergic and histamine containing synapses. These types of neurons are especially involved in transmission from the vestibular apparatus to the vomiting centre. Motion sickness principally involves overstimulation of these pathways due to various sensory stimuli. Hence the action of cyclizine which acts to block the histamine receptors in the vomiting centre and thus reduce activity along these pathways. Furthermore since cyclizine possesses anti-cholinergic properties as well, the muscarinic receptors are similarly blocked.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
UEstrogen sulfotransferase
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Cyclizine is metabolised to its N-demethylated derivative, norcyclizine, which has little antihistaminic (H1) activity compared to Cyclizine.

Route of elimination
Not Available
Half life

20 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Cyclizine 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 Cyclizine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Cyclizine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Cyclizine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Cyclizine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Cyclizine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Cyclizine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Cyclizine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Cyclizine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbexinostatThe risk or severity of QTc prolongation can be increased when Cyclizine is combined with Abexinostat.
AcebutololThe risk or severity of QTc prolongation can be increased when Cyclizine is combined with Acebutolol.
Food Interactions
  • Avoid alcohol.
  • Food may reduce irritation.
  • Take without regard to meals.

References

Synthesis Reference

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

General References
Not Available
External Links
Human Metabolome Database
HMDB0015307
KEGG Drug
D03621
KEGG Compound
C06930
PubChem Compound
6726
PubChem Substance
46506232
ChemSpider
6470
ChEBI
3994
ChEMBL
CHEMBL648
Therapeutic Targets Database
DAP000337
PharmGKB
PA164742937
Drugs.com
Drugs.com Drug Page
Wikipedia
Cyclizine
ATC Codes
R06AE03 — CyclizineR06AE53 — Cyclizine, combinations
MSDS
Download (73.4 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral25 mg/25mg
LiquidIntramuscular; Intravenous50 mg
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)105.5-107.5Baltzly, R. and Castillo, J.C.; U.S. Patent 2,630,435; March 3,1953; assigned to Burroughs Wellcome & Co. (U.S.A.) Inc.
water solubility1000 mg/L (at 25 °C)MERCK INDEX (1996); less than
logP3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0752 mg/mLALOGPS
logP3.55ALOGPS
logP3.55ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)8.51ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity84.93 m3·mol-1ChemAxon
Polarizability31.53 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9674
Blood Brain Barrier+0.9813
Caco-2 permeable+0.8023
P-glycoprotein substrateSubstrate0.8071
P-glycoprotein inhibitor INon-inhibitor0.7583
P-glycoprotein inhibitor IINon-inhibitor0.981
Renal organic cation transporterInhibitor0.7875
CYP450 2C9 substrateNon-substrate0.829
CYP450 2D6 substrateSubstrate0.6312
CYP450 3A4 substrateNon-substrate0.6591
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9676
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9438
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9071
Ames testNon AMES toxic0.9308
CarcinogenicityNon-carcinogens0.9667
BiodegradationNot ready biodegradable0.983
Rat acute toxicity2.3937 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6672
hERG inhibition (predictor II)Non-inhibitor0.5073
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0aos-9620000000-ed8810ea85a4b69f8507
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

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 / Aralkylamines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Diphenylmethane / Aralkylamine / N-alkylpiperazine / N-methylpiperazine / 1,4-diazinane / Piperazine / Tertiary amine / Tertiary aliphatic amine / Azacycle / Organoheterocyclic compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
N-alkylpiperazine (CHEBI:3994)

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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Leza JC, Lizasoain I, Lorenzo P: H1- and H2-histamine receptor blockers and opiate analgesia in mice. Methods Find Exp Clin Pharmacol. 1990 Dec;12(10):671-8. [PubMed:1983158]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sulfotransferase activity
Specific Function
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of estradiol and estrone. May play a role in the regulation of estrogen r...
Gene Name
SULT1E1
Uniprot ID
P49888
Uniprot Name
Estrogen sulfotransferase
Molecular Weight
35126.185 Da
References
  1. Bamforth KJ, Dalgliesh K, Coughtrie MW: Inhibition of human liver steroid sulfotransferase activities by drugs: a novel mechanism of drug toxicity? Eur J Pharmacol. 1992 May 1;228(1):15-21. [PubMed:1397064]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. He N, Zhang WQ, Shockley D, Edeki T: Inhibitory effects of H1-antihistamines on CYP2D6- and CYP2C9-mediated drug metabolic reactions in human liver microsomes. Eur J Clin Pharmacol. 2002 Feb;57(12):847-51. [PubMed:11936702]
  2. Auspar Cyclizine [File]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2018 20:30