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
Structure for Cyclizine (DB01176)
- 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).
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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 antagonistHumans UEstrogen sulfotransferase inhibitorHumans - 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
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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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Cyclizine is combined with 1,2-Benzodiazepine. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Cyclizine. 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. 
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- Avoid alcohol.
- Take with or without food. The absorption is unaffected by food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- 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 Canada 
- 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 US 
NAUSICALM TABLET 50MG (PHARMACY ONLY) Tablet 50 mg Oral APEX PHARMA MARKETING PTE. LTD. 2017-10-23 Not applicable Singapore - 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 Canada
Categories
- ATC Codes
- R06AE03 — Cyclizine
- 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
- 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 Tablet Oral 50 mg - 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) 8.2 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
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
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- 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
- 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
- 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]
Enzymes
- Kind
- Protein
- Organism
- Humans
- 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
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Regulator
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Martinez-Gomez MA, Carril-Aviles MM, Sagrado S, Villanueva-Camanas RM, Medina-Hernandez MJ: Characterization of antihistamine-human serum protein interactions by capillary electrophoresis. J Chromatogr A. 2007 Apr 20;1147(2):261-9. doi: 10.1016/j.chroma.2007.02.054. Epub 2007 Feb 22. [Article]
Drug created at June 13, 2005 13:24 / Updated at May 02, 2022 10:02