CYCLIZINE

US Approved OTC

First approved in 1953

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H22N2
Molecular Weight	266.3807
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCN(CC1)C(C2=CC=CC=C2)C3=CC=CC=C3

InChI

InChIKey=UVKZSORBKUEBAZ-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.medicines.org.uk/EMC/medicine/14672/SPC/Valoid+Tablets/
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/68003501

Cyclizine (cyclizine hydrochloride, Valoid®) is a histamine H1 antagonist of the piperazine class which is characterised by a low incidence of drowsiness. It possesses anticholinergic and antiemetic properties. The exact mechanism by which cyclizin (cyclizine hydrochloride, Valoid®) can prevent or suppress both nausea and vomiting from various causes is unknown. It increases lower oesophageal sphincter tone and reduces the sensitivity of the labyrinthine apparatus. It may inhibit the part of the midbrain known collectively as the emetic centre.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 313 Target ID: CHEMBL231 Sources: https://www.medicines.org.uk/emc/medicine/14672	Antagonist 2760		5.42 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Postoperative nausea and vomiting 29 Sources: https://www.medicines.org.uk/emc/medicine/14672	Preventing	Approved 8360	VALOID Approved Use Valoid is indicated for the prevention and treatment of nausea and vomiting including: • Motion sickness. • Nausea and vomiting caused by narcotic analgesics and by general anaesthetics in the post-operative period. • Vomiting associated with radiotherapy, especially for breast cancer since cyclizine does not elevate prolactin levels. Valoid may be of value in relieving vomiting and attacks of vertigo associated with Meniere's disease and other forms of vestibular disturbance. Launch Date 1.13365444E12
Motion sickness 43 Sources: https://www.medicines.org.uk/emc/medicine/14672	Preventing	Approved 8360	VALOID Approved Use Valoid is indicated for the prevention and treatment of nausea and vomiting including: • Motion sickness. • Nausea and vomiting caused by narcotic analgesics and by general anaesthetics in the post-operative period. • Vomiting associated with radiotherapy, especially for breast cancer since cyclizine does not elevate prolactin levels. Valoid may be of value in relieving vomiting and attacks of vertigo associated with Meniere's disease and other forms of vestibular disturbance. Launch Date 1.13365444E12
Vomiting associated with radiotherapy 4 Sources: https://www.medicines.org.uk/emc/medicine/14672	Preventing	Approved 8360	VALOID Approved Use Valoid is indicated for the prevention and treatment of nausea and vomiting including: • Motion sickness. • Nausea and vomiting caused by narcotic analgesics and by general anaesthetics in the post-operative period. • Vomiting associated with radiotherapy, especially for breast cancer since cyclizine does not elevate prolactin levels. Valoid may be of value in relieving vomiting and attacks of vertigo associated with Meniere's disease and other forms of vestibular disturbance. Launch Date 1.13365444E12

C_max

Value	Dose	Co-administered	Analyte	Population
90 ng/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/0928098796001777	18.682 mg single, intravenous dose: 18.682 mg route of administration: Intravenous experiment type: SINGLE co-administered:		CYCLIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
273.53 ng × h/mL EXPERIMENT https://www.sciencedirect.com/science/article/pii/0928098796001777	18.682 mg single, intravenous dose: 18.682 mg route of administration: Intravenous experiment type: SINGLE co-administered:		CYCLIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.53 h EXPERIMENT https://www.sciencedirect.com/science/article/pii/0928098796001777	18.682 mg single, intravenous dose: 18.682 mg route of administration: Intravenous experiment type: SINGLE co-administered:		CYCLIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
50 mg single, intravenous Recommended Dose: 50 mg Route: intravenous Route: single Dose: 50 mg Co-administed with:: morphine(10 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/12603456/	healthy, 34 years n = 1 Health Status: healthy Condition: pregnancy Age Group: 34 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/12603456/	Other AEs: Dystonic reaction... Other AEs: Dystonic reaction (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/12603456/
80 mg/kg single, oral Lethal dose Dose: 80 mg/kg Route: oral Route: single Dose: 80 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7062687/	unhealthy, children and adults Health Status: unhealthy Condition: nausea and vomiting Age Group: children and adults Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/7062687/	Disc. AE: Death... AEs leading to discontinuation/dose reduction: Death (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/7062687/
5 mg/kg single, oral Toxic dose Dose: 5 mg/kg Route: oral Route: single Dose: 5 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7062687/	unhealthy, children and adults n = 38 Health Status: unhealthy Condition: nausea and vomiting Age Group: children and adults Sex: unknown Population Size: 38 Sources: https://pubmed.ncbi.nlm.nih.gov/7062687/	Other AEs: Convulsions... Other AEs: Convulsions (38 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/7062687/

AEs

AE	Significance	Dose	Population
Dystonic reaction	1 patient	50 mg single, intravenous Recommended Dose: 50 mg Route: intravenous Route: single Dose: 50 mg Co-administed with:: morphine(10 mg) Sources: https://pubmed.ncbi.nlm.nih.gov/12603456/	healthy, 34 years n = 1 Health Status: healthy Condition: pregnancy Age Group: 34 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/12603456/
Death	grade 5 Disc. AE	80 mg/kg single, oral Lethal dose Dose: 80 mg/kg Route: oral Route: single Dose: 80 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7062687/	unhealthy, children and adults Health Status: unhealthy Condition: nausea and vomiting Age Group: children and adults Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/7062687/
Convulsions	38 patients	5 mg/kg single, oral Toxic dose Dose: 5 mg/kg Route: oral Route: single Dose: 5 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7062687/	unhealthy, children and adults n = 38 Health Status: unhealthy Condition: nausea and vomiting Age Group: children and adults Sex: unknown Population Size: 38 Sources: https://pubmed.ncbi.nlm.nih.gov/7062687/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1752	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 290 UGT2B4 249 UGT2B7 389 UGT2B10 127 UGT2B15 203 UGT2B17 213	MRP4 32 BCRP 75

Drug as perpetrator

Target	Modality	Activity
BCRP 765	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	yes
CYP2C9 1803	inhibitor 3240 Sources: https://livrepository.liverpool.ac.uk/15053/1/WilliamsonBet_Sep2013_15053.pdf#page=38 Page: 38.0	yes
MRP4 237	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A1 418	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT1A10 290	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT1A3 422	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT1A4 347	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT1A6 307	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT1A7 236	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT1A8 283	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT1A9 380	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT2B15 203	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT2B17 213	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT2B4 249	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT2B7 389	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	no
UGT2B10 127	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/29691239/	yes
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/22209223/	yes	yes (pharmacogenomic study) Comment: The median overall metabolic ratio at steady state was 4.9 (3.8-9.2) and did vary with CYP2D6 genotype (P=0.02). Sources: https://pubmed.ncbi.nlm.nih.gov/22209223/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3994	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3994
ZINC	ZINC000019156872	http://zinc15.docking.org/substances/ZINC000019156872
eMolecules	901706	https://www.emolecules.com/cgi-bin/more?vid=901706

PubMed

Title	Date	PubMed
Cyclizine anaphylaxis, when administered with propanidid.	1969 Jan	5762012
Dimenhydrinate (Dramamine) abuse: hallucinogenic experiences with a proprietary antihistamine.	1972 Feb	5058102
Cyclizine-induced chorea. Observations on the influence of cyclizine on dopamine-related movement disorders.	1977 Mar	839234
Effects of antihistaminics on locomotor activity in mice. Comparison with opiate and amphetamine-induced hyperactivity.	1991	1676005
Inhibitory effects of H1-antihistamines on CYP2D6- and CYP2C9-mediated drug metabolic reactions in human liver microsomes.	2002 Feb	11936702
Histamine H1-receptor antagonists, promethazine and homochlorcyclizine, increase the steady-state plasma concentrations of haloperidol and reduced haloperidol.	2003 Apr	12657913
Antihistamines in the treatment of dermatitis.	2003 Nov-Dec	15926215
Dystonic reaction to cyclizine.	2004 Apr	15023130
A capillary zone electrophoresis (CZE) method for the determination of cyclizine hydrochloride in tablets and suppositories.	2004 Apr 1	15030899
Is intraperitoneal levobupivacaine with epinephrine useful for analgesia following laparoscopic cholecystectomy? A randomized controlled trial.	2004 Aug	15473621
Improving the acceptability of the atrial defibrillator for the treatment of persistent atrial fibrillation: the atrial defibrillator sedation assessment study (ADSAS).	2004 Aug	15262026
Screening and semi-quantitative analysis of post mortem blood for basic drugs using gas chromatography/ion trap mass spectrometry.	2004 Dec 25	15556548
The Cyclimorph cough.	2004 Jun	15144309
Systematic review of the efficacy of antiemetics in the treatment of nausea in patients with far-advanced cancer.	2004 Jun	15108099
Spectrophotometric and LC determination of two binary mixtures containing antihistamins.	2004 Sep	15337437
Effect of (+) or (-) camphorsulfonic acid additives to the mobile phase on enantioseparations of some basic drugs on a Chiralcel OD column.	2005 Aug 12	16078699
Transient paralysis after administration of a single dose of cyclizine.	2005 Dec	16288623
An LC-MS-MS method for the determination of cyclizine in human serum.	2005 Sep 25	16054445
Acute eosinophilic pneumonia caused by calcium stearate, an additive agent for an oral antihistaminic medication.	2006	17016002
Prolonged extra-pyramidal side effects after discontinuation of haloperidol as an antiemetic.	2006 Apr	16764227
Transient paralysis after administration of cyclizine.	2006 Dec	17090261
Systematic review on the recurrence of postoperative nausea and vomiting after a first episode in the recovery room - implications for the treatment of PONV and related clinical trials.	2006 Dec 13	17166262
Best evidence topic report. Use of intravenous cyclizine in cardiac chest pain.	2006 Jan	16373808
Use of intravenous cyclizine in cardiac chest pain.	2006 Jul	16794116
Drugs for preventing postoperative nausea and vomiting.	2006 Jul 19	16856030
A comparison of cyclizine and granisetron alone and in combination for the prevention of postoperative nausea and vomiting.	2006 Nov	17042842
A preliminary ecotoxicity study of pharmaceuticals in the marine environment.	2006 Nov	16982534
Characterization of antihistamine-human serum protein interactions by capillary electrophoresis.	2007 Apr 20	17339039
Akathisia and an unusual symptomatic treatment: a case report.	2007 Dec	18073258
Routine multimodal antiemesis including low-dose perphenazine in an ambulatory surgery unit of a university hospital: a 10-year history. Supplement to: Eliminating postoperative nausea and vomiting in outpatient surgery with multimodal strategies including low doses of nonsedating, off-patent antiemetics: is "zero tolerance" achievable?	2007 Jun 12	17619779
Eliminating postoperative nausea and vomiting in outpatient surgery with multimodal strategies including low doses of nonsedating, off-patent antiemetics: is "zero tolerance" achievable?	2007 Jun 12	17619778
Management of Ménière's disease in general practice: adherence to the UK National Health Service 'Prodigy' guidelines.	2008 Aug	18039416
Chemotherapy-and cancer-related nausea and vomiting.	2008 Jan	18231647
The misuse/abuse of antihistamine antiemetic medication (cyclizine) by cancer patients.	2008 Oct	18718990
Mechanistic investigation of N,N-diethyl-4-(phenyl-piperidin-4-ylidenemethyl)-benzamide-induced insulin depletion in the rat and RINm5F cells.	2008 Sep	18539914
A survey of post-craniotomy analgesia in British neurosurgical centres: time for perceptions and prescribing to change?	2009	19863401
Application of adsorptive voltammetry for the detection of sub-nano molar cyclizine in biological fluids and tablets using fast Fourier transform continuous cyclic voltammetry in a flowing system.	2009 Apr	19359790
Morphine-induced hallucinations - resolution with switching to oxycodone: a case report and review of the literature.	2009 Dec 23	20062554
Management of postoperative nausea and vomiting: focus on palonosetron.	2009 Feb	19436621
Effect of fluid preloading on postoperative nausea and vomiting following laparoscopic cholecystectomy.	2009 Jul	20532102
Synthesis and in vitro antiproliferative activity of novel 1-benzhydrylpiperazine derivatives against human cancer cell lines.	2009 Mar	18973966
The cautious use of cyclizine in a patient with myasthenia gravis.	2009 Oct	19807233
Drugs associated with more suicidal ideations are also associated with more suicide attempts.	2009 Oct 2	19798416
Inappropriate prescribing in the hospitalized elderly patient: defining the problem, evaluation tools, and possible solutions.	2010 Apr 7	20396637
Optimal management of nausea and vomiting of pregnancy.	2010 Aug 4	21151729
Delayed ethylene glycol poisoning presenting with abdominal pain and multiple cranial and peripheral neuropathies: a case report.	2010 Jul 21	20663174
Neuropharmacology of vestibular system disorders.	2010 Mar	20808544
Palliative management of malignant bowel obstruction in terminally ill patient.	2010 May	21811356
Prescribing for migraine with the focus on selective 5HT1-receptor agonists: a pharmacy database analysis.	2010 May	20420788
Boosting blood flow: intravenous cyclizine in microsurgery.	2010 Sep	20811206

Patents

Sample Use Guides

In Vivo Use Guide

1 tablet (50 mg) orally, which may be repeated up to three times a day.

Route of Administration: Oral

In Vitro Use Guide

Cyclizine was tested for its effect on anti-IgE-induced histamine release from human lung fragments in vitro. IC50 value was 5.42 uM (0.14-20.44).

Name

Type

Language

CYCLIZINE

Official Name

English

CYCLIZINE [MART.]

Common Name

English

CYCLIZINE [HSDB]

Common Name

English

CYCLIZINE [MI]

Common Name

English

1-(Diphenylmethyl)-4-methylpiperazine

Systematic Name

English

cyclizine [INN]

Common Name

English

CYCLIZINE [VANDF]

Common Name

English

Cyclizine [WHO-DD]

Common Name

English

PIPERAZINE, 1-(DIPHENYLMETHYL)-4-METHYL-

Systematic Name

English

NSC-26608

Code

English

Classification Tree Code System Code

WHO-ESSENTIAL MEDICINES LIST

8.4