CLEMASTINE

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 Search

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
Sources: http://www.drugbank.ca/drugs/DB00283
Curator's Comment:: 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	Condition	Potency
Trypanosoma cruzi 8 Target ID: CHEMBL368 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25033456	Inhibitor 7701		0.400000000000000022 µM [IC50]
HERG 90 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16288909	Inhibitor 7701		12 nM [IC50]
Cytochrome P450 2D6 59 Target ID: CHEMBL289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9616188	Inhibitor 7701		2 µM [Ki]
Histamine H1 receptor 300 Target ID: CHEMBL231 Sources: http://www.drugbank.ca/drugs/DB00283	Antagonist 2577	Allergic rhinitis Urticaria

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic rhinitis 100 Sources: https://www.drugs.com/pro/clemastine.html	Primary	Histamine H1 receptor	Approved 7997	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 703728000000
Urticaria 39 Sources: https://www.drugs.com/pro/clemastine.html	Primary	Histamine H1 receptor	Approved 7997	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 703728000000

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 1421	inhibitor 1360

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1089

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1455	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/9616188/	yes [Ki 2 uM]
P-gp 1255	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/27279987/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1392	inhibitor 1374 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
ZINC	ZINC000000402830	http://zinc15.docking.org/substances/ZINC000000402830

PubMed

Title	Date	PubMed
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
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
Antihistamines in the treatment of dermatitis.	2003 Nov-Dec	15926215
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
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
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Rituximab treatment in patients with primary Sjögren's syndrome: an open-label phase II study.	2005 Sep	16142737
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
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
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
[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
Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial).	2008 Aug 22	18721465
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
Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response.	2008 Jul	17965121
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
Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS).	2008 Nov 26	19036143
Canine African trypanosoma.	2008 Sep	18811787
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
Application of prolonged microdialysis sampling in carboplatin-treated cancer patients.	2009 Aug	19096847
Ebastine in the light of CONGA recommendations for the development of third-generation antihistamines.	2009 Aug 31	21437146
Acute cough: a diagnostic and therapeutic challenge.	2009 Dec 16	20015366
Psoriasis vulgaris and digestive system disorders: is there a linkage?	2009 Jan	20164041
[Documentation for acute treatment with clemastine (Tavegyl) is missing].	2009 Jul 22-Aug 4	19739446
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
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

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Allergic Rhinitis

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

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