U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H26ClNO
Molecular Weight 343.891
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLEMASTINE

SMILES

C[C@@](c1ccccc1)(c2ccc(cc2)Cl)OCC[C@@]3([H])CCCN3C

InChI

InChIKey=YNNUSGIPVFPVBX-NHCUHLMSSA-N
InChI=1S/C21H26ClNO/c1-21(17-7-4-3-5-8-17,18-10-12-19(22)13-11-18)24-16-14-20-9-6-15-23(20)2/h3-5,7-8,10-13,20H,6,9,14-16H2,1-2H3/t20-,21-/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including http://www.sciencedirect.com/topics/page/Clemastine and https://www.drugs.com/pro/clemastine.html

Clemastine is an antihistamine with anticholinergic (drying) and sedative side effects. Clemastine is a selective histamine H1 antagonist and binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. It is used for the relief of symptoms associated with allergic rhinitis such as sneezing, rhinorrhea, pruritus and acrimation. Also for the management of mild, uncomplicated allergic skin manifestations of urticaria and angioedema. Used as self-medication for temporary relief of symptoms associated with the common cold.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.4 µM [IC50]
12.0 nM [IC50]
2.0 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CLEMASTINE

Approved Use

Clemastine fumarate tablets are indicated for the relief of symptoms associated with allergic rhinitis such as sneezing, rhinorrhea, pruritus, and lacrimation. Clemastine fumarate tablets are also indicated for the relief of mild, uncomplicated allergic skin manifestations of urticaria and angioedema.

Launch Date

7.0372799E11
Primary
CLEMASTINE

Approved Use

Clemastine fumarate tablets are indicated for the relief of symptoms associated with allergic rhinitis such as sneezing, rhinorrhea, pruritus, and lacrimation. Clemastine fumarate tablets are also indicated for the relief of mild, uncomplicated allergic skin manifestations of urticaria and angioedema.

Launch Date

7.0372799E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.7 ng/mL
3 mg single, oral
dose: 3 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLEMASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
650 pg/mL
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLEMASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1010 pg/mL
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLEMASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4.2 ng × h/mL
3 mg single, oral
dose: 3 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLEMASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
15529 pg × h/mL
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLEMASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
26230 pg × h/mL
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLEMASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8 h
3 mg single, oral
dose: 3 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLEMASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
17.28 h
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLEMASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
23.94 h
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLEMASTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
4 mg single, oral
Highest studied dose
Dose: 4 mg
Route: oral
Route: single
Dose: 4 mg
Sources:
healthy
n = 24
Health Status: healthy
Sex: M
Population Size: 24
Sources:
0.5 mg single, oral
Dose: 0.5 mg
Route: oral
Route: single
Dose: 0.5 mg
Sources: Page: page 58
healthy
n = 32
Health Status: healthy
Sex: M+F
Population Size: 32
Sources: Page: page 58
Disc. AE: Itching, Rash...
AEs leading to
discontinuation/dose reduction:
Itching (1 patient)
Rash (1 patient)
Nausea (1 patient)
Pallor (1 patient)
Sources: Page: page 58
1 mg single, oral
Dose: 1 mg
Route: oral
Route: single
Dose: 1 mg
Sources: Page: page 58
healthy
n = 32
Health Status: healthy
Sex: M
Population Size: 32
Sources: Page: page 58
Disc. AE: Vomiting...
AEs leading to
discontinuation/dose reduction:
Vomiting (1 patient)
Sources: Page: page 58
AEs

AEs

AESignificanceDosePopulation
Itching 1 patient
Disc. AE
0.5 mg single, oral
Dose: 0.5 mg
Route: oral
Route: single
Dose: 0.5 mg
Sources: Page: page 58
healthy
n = 32
Health Status: healthy
Sex: M+F
Population Size: 32
Sources: Page: page 58
Nausea 1 patient
Disc. AE
0.5 mg single, oral
Dose: 0.5 mg
Route: oral
Route: single
Dose: 0.5 mg
Sources: Page: page 58
healthy
n = 32
Health Status: healthy
Sex: M+F
Population Size: 32
Sources: Page: page 58
Pallor 1 patient
Disc. AE
0.5 mg single, oral
Dose: 0.5 mg
Route: oral
Route: single
Dose: 0.5 mg
Sources: Page: page 58
healthy
n = 32
Health Status: healthy
Sex: M+F
Population Size: 32
Sources: Page: page 58
Rash 1 patient
Disc. AE
0.5 mg single, oral
Dose: 0.5 mg
Route: oral
Route: single
Dose: 0.5 mg
Sources: Page: page 58
healthy
n = 32
Health Status: healthy
Sex: M+F
Population Size: 32
Sources: Page: page 58
Vomiting 1 patient
Disc. AE
1 mg single, oral
Dose: 1 mg
Route: oral
Route: single
Dose: 1 mg
Sources: Page: page 58
healthy
n = 32
Health Status: healthy
Sex: M
Population Size: 32
Sources: Page: page 58
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Ki 2 uM]
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
High-performance liquid chromatographic-tandem mass spectrometric method for the determination of ethionamide in human plasma, bronchoalveolar lavage fluid and alveolar cells.
2001 Apr 5
The effect of betahistine on vestibular habituation: comparison of rotatory and sway habituation training.
2001 Jul
Simultaneous screening and quantitation of 18 antihistamine drugs in blood by liquid chromatography ionspray tandem mass spectrometry.
2001 Sep 15
Phase II study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer.
2002 Mar 4
Antihistamines in the management of canine atopic dermatitis: a retrospective study of 171 dogs (1992-1998).
2002 Spring
Pharmacokinetics and pharmacodynamics of clemastine in healthy horses.
2003 Apr
Efficacy and safety of clemastine-pseudoephedrine-acetaminophen versus pseudoephedrine-acetaminophen in the treatment of seasonal allergic rhinitis in a 1-day, placebo-controlled park study.
2003 Jan
Antihistamines in the treatment of dermatitis.
2003 Nov-Dec
Identification of some new clemastine metabolites in dog, horse, and human urine with liquid chromatography/tandem mass spectrometry.
2004
Clinical pharmacology of clemastine in healthy dogs.
2004 Jun
Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic.
2004 Mar
Anaphylactic reaction and unrelated, subsequent, known side effects during therapy with thiethylperazine.
2005 Aug
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Inhibition of mast cell degranulation-induced drop of blood pressure with clemastine, cromolyn and compound 48/80 pretreatment.
2006 Apr
Dermatopathic lymphadenopathy: a differential diagnosis of enlarged lymph nodes in uremic pruritus.
2006 Dec
Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia.
2006 Dec
Clemastine, a conventional antihistamine, is a high potency inhibitor of the HERG K+ channel.
2006 Jan
[Diagnostic image (283). A man with a swollen tongue].
2006 Jul 22
Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab: the NEAR protocol (NCT00115518).
2006 May 8
[Pharmacological analysis of anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation].
2006 Nov-Dec
Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer.
2006 Oct 9
A novel self-microemulsifying formulation of paclitaxel for oral administration to patients with advanced cancer.
2006 Sep 18
Pharmacological prevention of serious anaphylactic reactions due to iodinated contrast media: systematic review.
2006 Sep 30
Influence of immunomodulatory drugs on the cytotoxicity induced by monoclonal antibody 17-1A and interleukin-2.
2007 Mar
Intraoperative anaphylaxis after intravenous atropine.
2007 Mar
[Angioneurotic orolingual edema associated with the use of rt-PA following a stroke].
2007 Oct
Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial).
2008 Aug 22
Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response.
2008 Jul
Medication with antihistamines impairs allergen-specific immunotherapy in mice.
2008 Mar
Canine African trypanosoma.
2008 Sep
Evaluation of efficacy and sedative profiles of H(1) antihistamines by large-scale surveillance using the visual analogue scale (VAS).
2008 Sep
A similarity search using molecular topological graphs.
2009
Clinical practice. Diagnosis and treatment of cow's milk allergy.
2009 Aug
Acute cough: a diagnostic and therapeutic challenge.
2009 Dec 16
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
Diagnostic approach identifying hydroxyethyl starch (HES) triggering a severe anaphylactic reaction during anesthesia in a 15-year-old boy.
2010 Dec
Treatment of locally advanced carcinomas of head and neck with intensity-modulated radiation therapy (IMRT) in combination with cetuximab and chemotherapy: the REACH protocol.
2010 Nov 26
A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours.
2010 Oct 26
Therapeutic efficacy of icatibant in angioedema induced by angiotensin-converting enzyme inhibitors: a case series.
2010 Sep
Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Allergic Rhinitis Initial dose: 1.34 mg orally twice a day. Dosage may be increased as required, but not to exceed 2.68 mg orally 3 times a day.
Route of Administration: Oral
IHERG tails at -40 mV following depolarizing pulses to +20 mV were inhibited by clemastine with an IC50 value of 12 nM in HEK 293 cells
Name Type Language
CLEMASTINE
INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
CLEMASTIN
Common Name English
CLEMASTINE [INN]
Common Name English
CLEMASTINE [WHO-DD]
Common Name English
CLEMASTINE [MI]
Common Name English
PYRROLIDINE, 2-(2-(1-(4-CHLOROPHENYL)-1-PHENYLETHOXY)ETHYL)-1-METHYL-, (R-(R*,R*))
Common Name English
HS-592
Code English
CLEMASTINE [USAN]
Common Name English
CLEMASTINE [VANDF]
Common Name English
(+)-(2R)-2-(-(((R)-P-CHLORO-.ALPHA.-METHYL-.ALPHA.-PHENYLBENZYL)OXY)ETHYL)-1-METHYLPYRROLIDINE
Common Name English
NSC-756685
Code English
Classification Tree Code System Code
WHO-VATC QD04AA14
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
WHO-VATC QR06AA04
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
LIVERTOX 216
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
WHO-ATC R06AA54
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
WHO-VATC QR06AA54
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
WHO-ATC D04AA14
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
NCI_THESAURUS C29578
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
WHO-ATC R06AA04
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
Code System Code Type Description
MESH
D002974
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
EVMPD
SUB06648MIG
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
RXCUI
2578
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY RxNorm
IUPHAR
6063
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
DRUG BANK
DB00283
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
EPA CompTox
15686-51-8
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
PUBCHEM
26987
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
NCI_THESAURUS
C61682
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
INN
2231
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
WIKIPEDIA
CLEMASTINE
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
MERCK INDEX
M3613
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY Merck Index
DRUG CENTRAL
671
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
ChEMBL
CHEMBL1626
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
LACTMED
Clemastine
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
CAS
15686-51-8
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY
FDA UNII
95QN29S1ID
Created by admin on Fri Jun 25 22:00:23 UTC 2021 , Edited by admin on Fri Jun 25 22:00:23 UTC 2021
PRIMARY