CLEMASTINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H26ClNO
Molecular Weight	343.89
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCC[C@@H]1CCO[C@](C)(C2=CC=CC=C2)C3=CC=C(Cl)C=C3

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
Sources: http://www.drugbank.ca/drugs/DB00283
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Trypanosoma cruzi 12 Target ID: CHEMBL368 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25033456	Inhibitor 8504	0.4 µM [IC50]
HERG 99 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16288909	Inhibitor 8504	12.0 nM [IC50]
Cytochrome P450 2D6 62 Target ID: CHEMBL289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9616188	Inhibitor 8504	2.0 µM [Ki]
Histamine H1 receptor 316 Target ID: CHEMBL231 Sources: http://www.drugbank.ca/drugs/DB00283	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic rhinitis 104 Sources: https://www.drugs.com/pro/clemastine.html	Primary		Approved 8583	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 1992
Urticaria 39 Sources: https://www.drugs.com/pro/clemastine.html	Primary		Approved 8583	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 1992

C_max

Value	Dose	Analyte	Population
0.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15664345/	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	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

Value	Dose	Analyte	Population
4.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15664345/	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	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

T_1/2

Value	Dose	Analyte	Population
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15664345/	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_biopharmr.pdf	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

Dose	Population	Adverse events
4 mg single, oral Highest studied dose Dose: 4 mg Route: oral Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8930778	healthy Health Status: healthy Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/8930778	Sources: https://pubmed.ncbi.nlm.nih.gov/8930778
0.5 mg single, oral Dose: 0.5 mg Route: oral Route: single Dose: 0.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf	healthy Health Status: healthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf	Disc. AE: Itching, Rash... AEs leading to discontinuation/dose reduction: Itching (1 patient) Rash (1 patient) Nausea (1 patient) Pallor (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf
1 mg single, oral Dose: 1 mg Route: oral Route: single Dose: 1 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf	healthy Health Status: healthy Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf	Disc. AE: Vomiting... AEs leading to discontinuation/dose reduction: Vomiting (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf

AEs

AE	Significance	Dose	Population
Itching	1 patient Disc. AE	0.5 mg single, oral Dose: 0.5 mg Route: oral Route: single Dose: 0.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf	healthy Health Status: healthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf
Nausea	1 patient Disc. AE	0.5 mg single, oral Dose: 0.5 mg Route: oral Route: single Dose: 0.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf	healthy Health Status: healthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf
Pallor	1 patient Disc. AE	0.5 mg single, oral Dose: 0.5 mg Route: oral Route: single Dose: 0.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf	healthy Health Status: healthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf
Rash	1 patient Disc. AE	0.5 mg single, oral Dose: 0.5 mg Route: oral Route: single Dose: 0.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf	healthy Health Status: healthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf
Vomiting	1 patient Disc. AE	1 mg single, oral Dose: 1 mg Route: oral Route: single Dose: 1 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf	healthy Health Status: healthy Sex: M Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/9616188/	yes [Ki 2 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/27279987/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/16288909/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3738	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3738
ChemicalBook	CB3376056	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3376056
ZINC	ZINC000000402830	http://zinc15.docking.org/substances/ZINC000000402830

PubMed

Title	Date	PubMed
Atrial T (Ta) loop in dogs with or without atrial injury.	1976 May	1266718
Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum.	2002	12442916
[Comparative antihistamine and anti-allergic effects of various antihistamine preparations].	2002	11980129
[Stem cell factor production from cultured nasal epithelial cells--effect on SCF production by drugs].	2002 Feb	11905054
[Severe adverse event following iv administration of 10 ml 6% Dextran60 (0.6 g) in a healthy volunteer].	2002 Oct	12395173
Antihistamines in the management of canine atopic dermatitis: a retrospective study of 171 dogs (1992-1998).	2002 Spring	12050832
Pharmacokinetics and pharmacodynamics of clemastine in healthy horses.	2003 Apr	12667185
Role of histamine receptors in the regulation of edema and circulation postburn.	2003 Dec	14636750
IgA pemphigus occurring in a 1-month-old infant.	2003 Feb	12582378
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	12546342
Why aren't lower, effective, OTC doses available earlier by prescription?	2003 Jan	12503949
Hypersensitivity vasculitis induced by cefoperazone/sulbactam.	2003 Jan 3	12556245
[Tolerance induction in anaphylaxis to carboplatin].	2003 Jul 25	12884147
Serious allergic reaction to administration of epirubicin.	2003 Jun	12948166
Fatal outcome of a hypersensitivity reaction to paclitaxel: a critical review of premedication regimens.	2004 Jan 26	14974481
[Appearance diagnosis. Facial shingles].	2004 Jul 22	15540566
Itch and skin rash from chocolate during fluoxetine and sertraline treatment: case report.	2004 Nov 2	15522120
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Simultaneous determination of ten antihistamine drugs in human plasma using pipette tip solid-phase extraction and gas chromatography/mass spectrometry.	2006	16419026
Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a dog.	2006 Mar	16434861
Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study.	2006 Mar 13	16465191
Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial).	2008 Aug 22	18721465
Major determinants and long-term outcomes of successful balloon dilatation for the pediatric patients with isolated native valvular pulmonary stenosis: a 10-year institutional experience.	2008 Jun 30	18581591
Medication with antihistamines impairs allergen-specific immunotherapy in mice.	2008 Mar	18081882
Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS).	2008 Nov 26	19036143
Evaluation of efficacy and sedative profiles of H(1) antihistamines by large-scale surveillance using the visual analogue scale (VAS).	2008 Sep	18566547
[Documentation for acute treatment with clemastine (Tavegyl) is missing].	2009 Jul 22-Aug 4	19739446
Psychoactive medication and traffic safety.	2009 Mar	19440432
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
Use of venlafaxine compared with other antidepressants and the risk of sudden cardiac death or near death: a nested case-control study.	2010 Feb 5	20139216

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

In Vitro Use Guide

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

HS-592

Preferred Name

English

CLEMASTINE

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

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