Cyclizine

Identification

Summary

Cyclizine is an antihistamine and antiemetic drug used for the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness, and vertigo.

Generic Name

Cyclizine

DrugBank Accession Number

DB01176

Background

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)

Type

Small Molecule

Groups

Approved

Structure

3D

Download

MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Cyclizine (DB01176)

×

Close

Weight

Average: 266.3807
Monoisotopic: 266.178298714

Chemical Formula

C₁₈H₂₂N₂

Synonyms

• (±)-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

Pharmacology

Indication

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

Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:

Machine Learning

Data Science

Drug Discovery

Accelerate your drug discovery research with our fully connected ADMET dataset

Learn more

Associated Conditions

• Migraine
• Motion Sickness

Contraindications & Blackbox Warnings

Contraindications & Blackbox Warnings

With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.

Learn more

Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects

Learn more

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.

Target	Actions	Organism
AHistamine H1 receptor	antagonist	Humans
UEstrogen sulfotransferase	inhibitor	Humans

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

Adverse Effects

Reduce medical errors

and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.

Learn more

Reduce medical errors & improve treatment outcomes with our adverse effects data

Learn more

Toxicity

Not Available

Pathways

Pathway	Category
Cyclizine H1-Antihistamine Action	Drug action

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Integrate drug-drug interactions in your software
1,2-Benzodiazepine	The risk or severity of adverse effects can be increased when Cyclizine is combined with 1,2-Benzodiazepine.
Acenocoumarol	The metabolism of Acenocoumarol can be decreased when combined with Cyclizine.
Acetazolamide	The risk or severity of adverse effects can be increased when Acetazolamide is combined with Cyclizine.
Acetohexamide	The metabolism of Acetohexamide can be decreased when combined with Cyclizine.
Acetophenazine	The risk or severity of adverse effects can be increased when Acetophenazine is combined with Cyclizine.
Acetylsalicylic acid	The metabolism of Acetylsalicylic acid can be decreased when combined with Cyclizine.
Aclidinium	Cyclizine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
Acrivastine	The risk or severity of QTc prolongation can be increased when Cyclizine is combined with Acrivastine.
Adenosine	The risk or severity of QTc prolongation can be increased when Cyclizine is combined with Adenosine.
Agomelatine	The risk or severity of adverse effects can be increased when Cyclizine is combined with Agomelatine.

Improve patient outcomes

Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.

Learn more

Food Interactions

• Avoid alcohol.
• Take with or without food. The absorption is unaffected by food.

Products

Comprehensive & structured drug product info

From application numbers to product codes, connect different identifiers through our commercial datasets.

Learn more

Easily connect various identifiers back to our datasets

Learn more

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Cyclizine hydrochloride	W0O1NHP4WE	303-25-3	UKPBEPCQTDRZSE-UHFFFAOYSA-N
Cyclizine lactate	861R00J986	5897-19-8	JOROEVAWQLGPFQ-UHFFFAOYSA-N

International/Other Brands

Emoquil / Marezine / Marzine (GlaxoSmithKline) / Valoid (GlaxoSmithKline)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Marzine Inj 50mg/ml	Liquid	50 mg / mL	Intramuscular; Intravenous	Glaxo Wellcome	1988-12-31	1998-07-30

Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Cyclivert	Tablet	25 mg/25mg	Oral	Laser Pharmaceuticals Llc	2011-11-01	2017-07-03

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Megral Tabs	Cyclizine hydrochloride (50 mg / tab) + Caffeine (100 mg / tab) + Ergotamine tartrate (2 mg / tab)	Tablet	Oral	Glaxo Wellcome	1989-12-31	2001-03-01

Categories

ATC Codes

R06AE03 — Cyclizine

• R06AE — Piperazine derivatives
• R06A — ANTIHISTAMINES FOR SYSTEMIC USE
• R06 — ANTIHISTAMINES FOR SYSTEMIC USE
• R — RESPIRATORY SYSTEM

R06AE53 — Cyclizine, combinations

• R06AE — Piperazine derivatives
• R06A — ANTIHISTAMINES FOR SYSTEMIC USE
• R06 — ANTIHISTAMINES FOR SYSTEMIC USE
• R — RESPIRATORY SYSTEM

Drug Categories

• Antiemetics
• Antihistamines for Systemic Use
• Autonomic Agents
• Central Nervous System Agents
• Central Nervous System Depressants
• Cytochrome P-450 CYP2C9 Inhibitors
• Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
• Cytochrome P-450 Enzyme Inhibitors
• Gastrointestinal Agents
• Histamine Agents
• Histamine Antagonists
• Histamine H1 Antagonists
• Neurotransmitter Agents
• Peripheral Nervous System Agents
• Piperazine Derivatives
• Piperazines
• Potential QTc-Prolonging Agents
• QTc Prolonging Agents

Chemical TaxonomyProvided by Classyfire

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

1,4-diazinane / Amine / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Diphenylmethane / Hydrocarbon derivative / N-alkylpiperazine / N-methylpiperazine / Organic nitrogen compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

N-alkylpiperazine (CHEBI:3994)

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

QRW9FCR9P2

CAS number

82-92-8

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

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

RxNav

2977

ChEBI

3994

ChEMBL

CHEMBL648

ZINC

ZINC000019156872

Therapeutic Targets Database

DAP000337

PharmGKB

PA164742937

Drugs.com

Drugs.com Drug Page

Wikipedia

Cyclizine

MSDS

Download (73.4 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
Not Available	Not Yet Recruiting	Treatment	Spinal Anesthetics Causing Adverse Effects in Therapeutic Use	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet	Oral	25 mg/25mg
Tablet, coated	Oral
Tablet, sugar coated	Oral
Tablet	Oral
Liquid	Intramuscular; Intravenous	50 mg / mL
Tablet	Oral

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	105.5-107.5	Baltzly, R. and Castillo, J.C.; U.S. Patent 2,630,435; March 3,1953; assigned to Burroughs Wellcome & Co. (U.S.A.) Inc.
water solubility	1000 mg/L (at 25 °C)	MERCK INDEX (1996); less than
logP	3	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0752 mg/mL	ALOGPS
logP	3.55	ALOGPS
logP	3.55	ChemAxon
logS	-3.6	ALOGPS
pKa (Strongest Basic)	8.51	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	6.48 Å2	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	84.93 m3·mol-1	ChemAxon
Polarizability	31.53 Å3	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9674
Blood Brain Barrier	+	0.9813
Caco-2 permeable	+	0.8023
P-glycoprotein substrate	Substrate	0.8071
P-glycoprotein inhibitor I	Non-inhibitor	0.7583
P-glycoprotein inhibitor II	Non-inhibitor	0.981
Renal organic cation transporter	Inhibitor	0.7875
CYP450 2C9 substrate	Non-substrate	0.829
CYP450 2D6 substrate	Substrate	0.6312
CYP450 3A4 substrate	Non-substrate	0.6591
CYP450 1A2 substrate	Non-inhibitor	0.9046
CYP450 2C9 inhibitor	Non-inhibitor	0.9676
CYP450 2D6 inhibitor	Inhibitor	0.8931
CYP450 2C19 inhibitor	Non-inhibitor	0.9026
CYP450 3A4 inhibitor	Non-inhibitor	0.9438
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9071
Ames test	Non AMES toxic	0.9308
Carcinogenicity	Non-carcinogens	0.9667
Biodegradation	Not ready biodegradable	0.983
Rat acute toxicity	2.3937 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.6672
hERG inhibition (predictor II)	Non-inhibitor	0.5073

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
GC-MS Spectrum - EI-B	GC-MS	splash10-0aos-9620000000-ed8810ea85a4b69f8507
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Targets

Accelerate your drug discovery research

with our fully connected ADMET & drug target dataset.

Learn more

Accelerate your drug discovery research with our ADMET & drug target dataset

Learn more

Details1. Histamine H1 receptor

Kind

Protein

Organism

Humans

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. [Article]
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. [Article]

Details2. Estrogen sulfotransferase

Kind

Protein

Organism

Humans

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. [Article]

×

Improve patient outcomes

Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.

Learn more

Drug created on June 13, 2005 13:24 / Updated on June 12, 2021 10:52