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 9 Target ID: CHEMBL368 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25033456	Inhibitor 8146	0.4 µM [IC50]
HERG 91 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16288909	Inhibitor 8146	12.0 nM [IC50]
Cytochrome P450 2D6 61 Target ID: CHEMBL289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9616188	Inhibitor 8146	2.0 µM [Ki]
Histamine H1 receptor 312 Target ID: CHEMBL231 Sources: http://www.drugbank.ca/drugs/DB00283	Antagonist 2737

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic rhinitis 100 Sources: https://www.drugs.com/pro/clemastine.html	Primary		Approved 8307	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 38 Sources: https://www.drugs.com/pro/clemastine.html	Primary		Approved 8307	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 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1401

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/9616188/	yes [Ki 2 uM]
P-gp 1588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/27279987/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 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
Evaluation of several solid phase extraction liquid chromatography/tandem mass spectrometry on-line configurations for high-throughput analysis of acidic and basic drugs in rat plasma.	2001	11404844
Inhibitory effect of olopatadine hydrochloride on the sneezing response induced by intranasal capsaicin challenge in guinea pigs.	2001 Jun	11459132
Dose reduction of steroid premedication for paclitaxel: no increase of hypersensitivity reactions.	2001 Jun	11455223
[Comparative antihistamine and anti-allergic effects of various antihistamine preparations].	2002	11980129
[Severe adverse event following iv administration of 10 ml 6% Dextran60 (0.6 g) in a healthy volunteer].	2002 Oct	12395173
Hypersensitivity vasculitis induced by cefoperazone/sulbactam.	2003 Jan 3	12556245
Identification of some new clemastine metabolites in dog, horse, and human urine with liquid chromatography/tandem mass spectrometry.	2004	15384147
Interstitial granulomatous dermatitis with arthritis.	2004 Jul	15257555
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
Clemastine, a conventional antihistamine, is a high potency inhibitor of the HERG K+ channel.	2006 Jan	16288909
[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
Early detection of adverse drug events within population-based health networks: application of sequential testing methods.	2007 Dec	17955500
Intraoperative anaphylaxis after intravenous atropine.	2007 Mar	17087843
Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial).	2008 Aug 22	18721465
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
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
Evaluation of efficacy and sedative profiles of H(1) antihistamines by large-scale surveillance using the visual analogue scale (VAS).	2008 Sep	18566547
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
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
Chloroquine-induced Pruritus.	2010 May	21188034

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 `Fri Dec 16 16:46:33 UTC 2022` Edited by `admin` on `Fri Dec 16 16:46:33 UTC 2022`
Record UNII	95QN29S1ID
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

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

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