You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameCyclizine
Accession NumberDB01176  (APRD00061)
TypeSmall Molecule
GroupsApproved
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
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Marzine Inj 50mg/mlliquid50 mgintramuscular; intravenousGlaxo Wellcome Inc.1988-12-311998-07-30Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cycliverttablet25 mg/25mgoralLaser Pharmaceuticals, LLC2011-11-01Not applicableUs
Unapproved/Other Products Not Available
International Brands
NameCompany
EmoquilNot Available
MarezineNot Available
MarzineGlaxoSmithKline
ValoidGlaxoSmithKline
Brand mixtures
NameLabellerIngredients
Megral TabsGlaxo Wellcome Inc.
Salts
Name/CASStructureProperties
Cyclizine chloride
Thumb
  • InChI Key: UKPBEPCQTDRZSE-UHFFFAOYSA-N
  • Monoisotopic Mass: 302.154976453
  • Average Mass: 302.842
DBSALT000399
Cyclizine hydrochloride
ThumbNot applicableDBSALT001535
Cyclizine lactate
ThumbNot applicableDBSALT001182
Categories
UNIIQRW9FCR9P2
CAS number82-92-8
WeightAverage: 266.3807
Monoisotopic: 266.178298714
Chemical FormulaC18H22N2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Aralkylamine
  • N-alkylpiperazine
  • N-methylpiperazine
  • Piperazine
  • 1,4-diazinane
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness, and vertigo (dizziness caused by other medical problems).
PharmacodynamicsCyclizine 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 actionVomiting (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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

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

Route of eliminationNot Available
Half life20 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral25 mg/25mg
Liquidintramuscular; intravenous50 mg
Tabletoral
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point105.5-107.5Baltzly, 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-3.5ALOGPS
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 RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
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 ReferencesNot Available
External Links
ATC CodesR06AE03R06AE53
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73.4 KB)
Interactions
Drug Interactions
Drug
AclidiniumAclidinium may increase the anticholinergic activities of Cyclizine.
AmphetamineAmphetamine may decrease the sedative activities of Cyclizine.
AzelastineCyclizine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Cyclizine.
Benzylpenicilloyl PolylysineCyclizine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Cyclizine.
Botulinum Toxin Type ACyclizine may increase the anticholinergic activities of Botulinum Toxin Type A.
Botulinum Toxin Type BCyclizine may increase the anticholinergic activities of Botulinum Toxin Type B.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
BuprenorphineCyclizine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
CathinoneCathinone may decrease the sedative activities of Cyclizine.
CimetropiumCyclizine may increase the anticholinergic activities of Cimetropium Bromide.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
EluxadolineCyclizine may increase the activities of Eluxadoline.
EthanolCyclizine may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
Glucagon recombinantThe risk or severity of adverse effects can be increased when Cyclizine is combined with Glucagon recombinant.
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Cyclizine.
HydrocodoneCyclizine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
Ipratropium bromideIpratropium bromide may increase the anticholinergic activities of Cyclizine.
ItoprideThe therapeutic efficacy of Itopride can be decreased when used in combination with Cyclizine.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Cyclizine.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
MethotrimeprazineCyclizine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
MetyrosineCyclizine may increase the sedative activities of Metyrosine.
MianserinMianserin may increase the anticholinergic activities of Cyclizine.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
MirabegronThe risk or severity of adverse effects can be increased when Cyclizine is combined with Mirabegron.
MirtazapineCyclizine may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
MorphineThe risk or severity of adverse effects can be increased when Cyclizine is combined with Morphine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
OrphenadrineCyclizine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
ParaldehydeCyclizine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineThe risk or severity of adverse effects can be increased when Cyclizine is combined with Paroxetine.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
Potassium ChlorideCyclizine may increase the ulcerogenic activities of Potassium Chloride.
PramipexoleCyclizine may increase the sedative activities of Pramipexole.
PramlintidePramlintide may increase the anticholinergic activities of Cyclizine.
ProcyclidineThe risk or severity of adverse effects can be increased when Procyclidine is combined with Cyclizine.
RamosetronCyclizine may increase the activities of Ramosetron.
RopiniroleCyclizine may increase the sedative activities of Ropinirole.
RotigotineCyclizine may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Cyclizine.
SecretinThe therapeutic efficacy of Secretin can be decreased when used in combination with Cyclizine.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
SulpirideThe therapeutic efficacy of Sulpiride can be decreased when used in combination with Cyclizine.
SuvorexantCyclizine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TacrineThe therapeutic efficacy of Cyclizine can be decreased when used in combination with Tacrine.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Cyclizine.
ThalidomideCyclizine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
TiotropiumCyclizine may increase the anticholinergic activities of Tiotropium.
TopiramateThe risk or severity of adverse effects can be increased when Cyclizine is combined with Topiramate.
TrichlormethiazideThe serum concentration of Trichlormethiazide can be increased when it is combined with Cyclizine.
UmeclidiniumUmeclidinium may increase the anticholinergic activities of Cyclizine.
ZolpidemCyclizine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food Interactions
  • Avoid alcohol.
  • Food may reduce irritation.
  • Take without regard to meals.

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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
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 receptor activity by metabolizing free estradiol. Maximally sulfates beta-estradiol and estrone at concentrations of 20 nM. Also sulfates dehydroepiandrosterone, pregnenolone, ethinylestradiol, equalen...
Gene Name:
SULT1E1
Uniprot ID:
P49888
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23