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

Molecular Formula	C21H26ClNO
Molecular Weight	343.89
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

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
Interactions of olopatadine and selected antihistamines with model and natural membranes.	2003 Dec	14704897
Role of histamine receptors in the regulation of edema and circulation postburn.	2003 Dec	14636750
Serious allergic reaction to administration of epirubicin.	2003 Jun	12948166
Antihistamines in the treatment of dermatitis.	2003 Nov-Dec	15926215
Identification of some new clemastine metabolites in dog, horse, and human urine with liquid chromatography/tandem mass spectrometry.	2004	15384147
Fatal outcome of a hypersensitivity reaction to paclitaxel: a critical review of premedication regimens.	2004 Jan 26	14974481
Interstitial granulomatous dermatitis with arthritis.	2004 Jul	15257555
[Appearance diagnosis. Facial shingles].	2004 Jul 22	15540566
Clinical pharmacology of clemastine in healthy dogs.	2004 Jun	15214951
Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic.	2004 Mar	15049392
Pegylated liposomal doxorubicin in combination with mitomycin C, infusional 5-fluorouracil and sodium folinic acid. A phase-I-study in patients with upper gastrointestinal cancer.	2004 May 17	15138468
Itch and skin rash from chocolate during fluoxetine and sertraline treatment: case report.	2004 Nov 2	15522120
[Multilocular painful urticarial plaques. Eosinophilic cellulitis (Wells syndrome)].	2004 Oct 27	15559909
Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas.	2005	16168106
Anaphylactic reaction and unrelated, subsequent, known side effects during therapy with thiethylperazine.	2005 Aug	16101941
High-performance liquid chromatographic-tandem mass spectrometric method for the determination of clemastine in human plasma.	2005 Feb 25	15664345
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
First-line therapy with gemcitabine and paclitaxel in locally, recurrent or metastatic breast cancer: a phase II study.	2005 Nov 29	16316459
[Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs)].	2005 Oct 7	16208597
Rituximab treatment in patients with primary Sjögren's syndrome: an open-label phase II study.	2005 Sep	16142737
Evaluation of the rabbit Purkinje fibre assay as an in vitro tool for assessing the risk of drug-induced torsades de pointes in humans.	2006	16524323
Simultaneous determination of ten antihistamine drugs in human plasma using pipette tip solid-phase extraction and gas chromatography/mass spectrometry.	2006	16419026
The prevention of anaphylactoid reactions to iodinated radiological contrast media: a systematic review.	2006 Apr 27	16643668
Clemastine, a conventional antihistamine, is a high potency inhibitor of the HERG K+ channel.	2006 Jan	16288909
Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma.	2006 Jun 19	16685263
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
Neoadjuvant concurrent chemoradiation with weekly paclitaxel and carboplatin for patients with oesophageal cancer: a phase II study.	2006 May 22	16670722
Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab: the NEAR protocol (NCT00115518).	2006 May 8	16681848
A novel self-microemulsifying formulation of paclitaxel for oral administration to patients with advanced cancer.	2006 Sep 18	16926835
Development and full validation of a sensitive quantitative assay for the determination of clemastine in human plasma by liquid chromatography-tandem mass spectrometry.	2007 Aug 15	17475437
[Emergency checklist: angioedema].	2007 Aug 2	17849784
Stereoselective synthesis of (-)-hydroxyclemastine as a versatile intermediate for the H1 receptor antagonist clemastine.	2007 Dec	18254238
Early detection of adverse drug events within population-based health networks: application of sequential testing methods.	2007 Dec	17955500
Psoriasis following growth hormone therapy in a child.	2007 Jan	17179190
Influence of immunomodulatory drugs on the cytotoxicity induced by monoclonal antibody 17-1A and interleukin-2.	2007 Mar	17562330
[Angioneurotic orolingual edema associated with the use of rt-PA following a stroke].	2007 Oct	17694290
Anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation: frequency and power dependence.	2008 Apr	18044738
[Chikungunya: fever and joint pains after vacation in a tropical area].	2008 Feb	18288627
A highly active and tolerable neoadjuvant regimen combining paclitaxel, carboplatin, 5-FU, and radiation therapy in patients with stage II and III esophageal cancer.	2008 Jan	17896144
Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response.	2008 Jul	17965121
Antagonist affinity measurements at the Gi-coupled human histamine H3 receptor expressed in CHO cells.	2008 Jun 6	18538007
Medication with antihistamines impairs allergen-specific immunotherapy in mice.	2008 Mar	18081882
Ebastine in the light of CONGA recommendations for the development of third-generation antihistamines.	2009 Aug 31	21437146
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
Diagnostic approach identifying hydroxyethyl starch (HES) triggering a severe anaphylactic reaction during anesthesia in a 15-year-old boy.	2010 Dec	20556705
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
Anaphylaxis to mefenamic acid in a patient with new onset of systemic lupus erythematosus.	2010 Jul-Aug	20153574
Synthesis of (-)-(S,S)-clemastine by invertive N --> C aryl migration in a lithiated carbamate.	2010 May 21	20405879
Structural elucidation of N-oxidized clemastine metabolites by liquid chromatography/tandem mass spectrometry and the use of Cunninghamella elegans to facilitate drug metabolite identification.	2010 May 30	20411584

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

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:53:45 GMT 2025` Edited by `admin` on `Mon Mar 31 17:53:45 GMT 2025`
Record UNII	95QN29S1ID
Record Status	`Validated (UNII)`
Record Version

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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