CLEMASTINE FUMARATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H26ClNO.C4H4O4
Molecular Weight	459.962
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C(O)=O.CN1CCC[C@@H]1CCO[C@](C)(C2=CC=CC=C2)C3=CC=C(Cl)C=C3

InChI

InChIKey=PMGQWSIVQFOFOQ-YKVZVUFRSA-N

InChI=1S/C21H26ClNO.C4H4O4/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;5-3(6)1-2-4(7)8/h3-5,7-8,10-13,20H,6,9,14-16H2,1-2H3;1-2H,(H,5,6)(H,7,8)/b;2-1+/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

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

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 11 Target ID: CHEMBL368 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25033456	Inhibitor 8228	0.4 µM [IC50]
HERG 91 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16288909	Inhibitor 8228	12.0 nM [IC50]
Cytochrome P450 2D6 61 Target ID: CHEMBL289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9616188	Inhibitor 8228	2.0 µM [Ki]
Histamine H1 receptor 313 Target ID: CHEMBL231 Sources: http://www.drugbank.ca/drugs/DB00283	Antagonist 2760

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic rhinitis 100 Sources: https://www.drugs.com/pro/clemastine.html	Primary		Approved 8360	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
Urticaria 39 Sources: https://www.drugs.com/pro/clemastine.html	Primary		Approved 8360	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

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 n = 24 Health Status: healthy Sex: M Population Size: 24 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 Page: page 58	healthy n = 32 Health Status: healthy Sex: M+F Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58
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 Page: page 58	healthy n = 32 Health Status: healthy Sex: M Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	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 Page: page 58

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 Page: page 58	healthy n = 32 Health Status: healthy Sex: M+F Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	healthy n = 32 Health Status: healthy Sex: M+F Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	healthy n = 32 Health Status: healthy Sex: M+F Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58	healthy n = 32 Health Status: healthy Sex: M+F Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58
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 Page: page 58	healthy n = 32 Health Status: healthy Sex: M Population Size: 32 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-082_Tavist_medr_P2.pdf Page: page 58

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1437

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/9616188/	yes [Ki 2 uM]
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/27279987/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 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
Identification of some new clemastine metabolites in dog, horse, and human urine with liquid chromatography/tandem mass spectrometry.	2004	15384147
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
[Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs)].	2005 Oct 7	16208597
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
Inhibition of mast cell degranulation-induced drop of blood pressure with clemastine, cromolyn and compound 48/80 pretreatment.	2006 Apr	16705372
The prevention of anaphylactoid reactions to iodinated radiological contrast media: a systematic review.	2006 Apr 27	16643668
Dermatopathic lymphadenopathy: a differential diagnosis of enlarged lymph nodes in uremic pruritus.	2006 Dec	17176922
Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia.	2006 Dec	17089107
[Diagnostic image (283). A man with a swollen tongue].	2006 Jul 22	16901065
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
[Pharmacological analysis of anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation].	2006 Nov-Dec	17175917
A novel self-microemulsifying formulation of paclitaxel for oral administration to patients with advanced cancer.	2006 Sep 18	16926835
Pharmacological prevention of serious anaphylactic reactions due to iodinated contrast media: systematic review.	2006 Sep 30	16880193
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
Histamine upregulates keratinocyte MMP-9 production via the histamine H1 receptor.	2008 Dec	18548114
[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
Spectrophotometric determination of some histamine H1-antagonists drugs in their pharmaceutical preparations.	2008 Jan	17553739
Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response.	2008 Jul	17965121
NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial).	2008 Jul 31	18671847
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
Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes.	2008 May	18265982
Evaluation of efficacy and sedative profiles of H(1) antihistamines by large-scale surveillance using the visual analogue scale (VAS).	2008 Sep	18566547
Clinical practice. Diagnosis and treatment of cow's milk allergy.	2009 Aug	19271238
Ebastine in the light of CONGA recommendations for the development of third-generation antihistamines.	2009 Aug 31	21437146
Psoriasis vulgaris and digestive system disorders: is there a linkage?	2009 Jan	20164041
Psychoactive medication and traffic safety.	2009 Mar	19440432
Hypersensitivity reactions associated with platinum antineoplastic agents: a systematic review.	2010	20886011
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
Hyperimmune anti-HBs plasma as alternative to commercial immunoglobulins for prevention of HBV recurrence after liver transplantation.	2010 Jul 4	20598161
Anaphylaxis to mefenamic acid in a patient with new onset of systemic lupus erythematosus.	2010 Jul-Aug	20153574
[Discriminant function analysis in the assessment of laboratory test data in the correction of traditional therapy for mild icteric form of viral hepatitis B in children with food allergy].	2010 Jun	20734860
Chloroquine-induced Pruritus.	2010 May	21188034
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
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	21108850
[Progress of study on antitumor effects of antibody dependent cell mediated cytotoxicity--review].	2010 Oct	21129296
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	20877350
Therapeutic efficacy of icatibant in angioedema induced by angiotensin-converting enzyme inhibitors: a case series.	2010 Sep	20447725

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 `Thu Jul 06 12:59:56 UTC 2023` Edited by `admin` on `Thu Jul 06 12:59:56 UTC 2023`
Record UNII	19259EGQ3D
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

CLEMASTINE FUMARATE

Official Name

English

Clemastine fumarate [WHO-DD]

Common Name

English

TAVIST

Brand Name

English

CLEMASTINE FUMARATE [MART.]

Common Name

English

CLEMASTINE FUMARATE [HSDB]

Common Name

English

CLEMASTINE FUMARATE [ORANGE BOOK]

Common Name

English

CLEMASTINE FUMARATE [USP MONOGRAPH]

Common Name

English

CLEMASTINE FUMARATE [VANDF]

Common Name

English

CLEMASTINE FUMARATE [EP MONOGRAPH]

Common Name

English

CLEMASTINE FUMARATE [JAN]

Common Name

English

CLEMASTINE FUMARATE COMPONENT OF TAVIST-D

Common Name

English

TAVIST-D COMPONENT CLEMASTINE FUMARATE

Common Name

English

PYRROLIDINE, 2-(2-(1-(4-CHLOROPHENYL)-1-PHENYLETHOXY)ETHYL)-1-METHYL-, (R-(R*,R*))-, (E)-2-BUTENEDIOATE (1:1)

Common Name

English

CLEMASTINE FUMARATE [USP-RS]

Common Name

English

CLEMASTINE HYDROGEN FUMARATE [MI]

Common Name

English

CLEMASTINE HYDROGEN FUMARATE

Common Name

English

(+)-(2R)-2-(2-(((R)-P-CHLORO-.ALPHA.-METHYL-.ALPHA.-PHENYLBENZYL)OXY)ETHYL)-1-METHYLPYRROLIDINE FUMARATE (1:1)

Common Name

English

CLEMASTINE FUMARATE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578