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Details

Stereochemistry ACHIRAL
Molecular Formula C18H22N2.2ClH
Molecular Weight 339.303
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CYCLIZINE DIHYDROCHLORIDE

SMILES

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

InChI

InChIKey=CKLJCUGYMOMAEJ-UHFFFAOYSA-N
InChI=1S/C18H22N2.2ClH/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;2*1H

HIDE SMILES / InChI
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C18H22N2
Molecular Weight 266.3807
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

1953
193
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
 5.42 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Approved
8429
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

2005
Preventing
Approved
8429
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

2005
Preventing
Approved
8429
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

2005
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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

AEs

AESignificanceDosePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1767
substrate
1217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
UGT1A1
418

UGT1A3
422

UGT1A4
347

UGT1A6
307

UGT1A7
236

UGT1A8
283

UGT1A9
380

UGT1A10
291

UGT2B4
249

UGT2B7
389

UGT2B10
127

UGT2B15
203

UGT2B17
213
MRP4
32

BCRP
75
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
BCRP
773
 yes
CYP2C9
1819
 yes
MRP4
238
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
UGT1A1
418
 no
UGT1A10
291
 no
UGT1A3
422
 no
UGT1A4
347
 no
UGT1A6
307
 no
UGT1A7
236
 no
UGT1A8
283
 no
UGT1A9
380
 no
UGT2B15
203
 no
UGT2B17
213
 no
UGT2B4
249
 no
UGT2B7
389
 no
UGT2B10
127
 yes
CYP2D6
1217
 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).
Sourcing

Sourcing

Vendor/AggregatorIDURL
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

PubMed

TitleDatePubMed
Cyclizine anaphylaxis, when administered with propanidid.
1969 Jan
Cyclizine-induced chorea. Observations on the influence of cyclizine on dopamine-related movement disorders.
1977 Mar
Effects of antihistaminics on locomotor activity in mice. Comparison with opiate and amphetamine-induced hyperactivity.
1991
Patterns of ergotamine and sumatriptan use in the Netherlands from 1991 to 1997.
2001 Jun
Pre-emptive metoclopramide and ondansetron for nausea and vomiting associated with iloprost infusions.
2001 Jun
Postoperative nausea management and patient-controlled analgesia.
2001 Jun 28-Jul 11
Precipitation in Manchester: ketorolac/cyclizine.
2001 May
Simultaneous screening and quantitation of 18 antihistamine drugs in blood by liquid chromatography ionspray tandem mass spectrometry.
2001 Sep 15
Inhibitory effects of H1-antihistamines on CYP2D6- and CYP2C9-mediated drug metabolic reactions in human liver microsomes.
2002 Feb
Comparison of cyclizine and ondansetron for the prevention of postoperative nausea and vomiting in laparoscopic day-case gynaecological surgery.
2002 Jan
Comparison of intrathecal fentanyl and diamorphine in addition to bupivacaine for caesarean section under spinal anaesthesia.
2002 Sep
Biotransformation of cyclizine in greyhounds. 2: N(1)-dealkylation and identification of some neutral and phenolic metabolites in canine urine by gas chromatography-mass spectrometry.
2002 Sep
Biotransformation of cyclizine in greyhounds. 1: Identification and analysis of cyclizine and some basic metabolites in canine urine by gas chromatography-mass spectrometry.
2002 Sep
Histamine H1-receptor antagonists, promethazine and homochlorcyclizine, increase the steady-state plasma concentrations of haloperidol and reduced haloperidol.
2003 Apr
Probable dystonic reaction after a single dose of cyclizine in a patient with a history of encephalitis.
2003 Mar
Prevention of postoperative nausea and vomiting after spinal morphine for Caesarean section: comparison of cyclizine, dexamethasone and placebo.
2003 May
Dystonic reaction to cyclizine.
2004 Apr
Is intraperitoneal levobupivacaine with epinephrine useful for analgesia following laparoscopic cholecystectomy? A randomized controlled trial.
2004 Aug
Screening and semi-quantitative analysis of post mortem blood for basic drugs using gas chromatography/ion trap mass spectrometry.
2004 Dec 25
Early analgesic effects of parecoxib versus ketorolac following laparoscopic sterilization: a randomized controlled trial.
2004 Jun
Diluent choice for subcutaneous infusion: a survey of the literature and Australian practice.
2005 Feb
Percutaneous absorption of cyclizine and its alkyl analogues.
2005 Feb
A comparison of cyclizine and granisetron alone and in combination for the prevention of postoperative nausea and vomiting.
2006 Nov
Characterization of antihistamine-human serum protein interactions by capillary electrophoresis.
2007 Apr 20
Chemotherapy-and cancer-related nausea and vomiting.
2008 Jan
Drugs associated with more suicidal ideations are also associated with more suicide attempts.
2009 Oct 2
Inappropriate prescribing in the hospitalized elderly patient: defining the problem, evaluation tools, and possible solutions.
2010 Apr 7
Delayed ethylene glycol poisoning presenting with abdominal pain and multiple cranial and peripheral neuropathies: a case report.
2010 Jul 21
Patents

Patents

JP2008526895A
32
JPH08225447A
10
US2630435
4

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).
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:58:01 GMT 2023
Edited
by admin
on Sat Dec 16 01:58:01 GMT 2023
Record UNII
VF601QVZ67
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CYCLIZINE DIHYDROCHLORIDE
Common Name English
PIPERAZINE, 1-(DIPHENYLMETHYL)-4-METHYL-, DIHYDROCHLORIDE
Common Name English
PIPERAZINE, 1-(DIPHENYLMETHYL)-4-METHYL-, HYDROCHLORIDE (1:2)
Systematic Name English
Code System Code Type Description
FDA UNII
VF601QVZ67
Created by admin on Sat Dec 16 01:58:01 GMT 2023 , Edited by admin on Sat Dec 16 01:58:01 GMT 2023
PRIMARY
PUBCHEM
67533
Created by admin on Sat Dec 16 01:58:01 GMT 2023 , Edited by admin on Sat Dec 16 01:58:01 GMT 2023
PRIMARY
CAS
5897-18-7
Created by admin on Sat Dec 16 01:58:01 GMT 2023 , Edited by admin on Sat Dec 16 01:58:01 GMT 2023
PRIMARY
NIH
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