Identification

Name
Clemastine
Accession Number
DB00283  (APRD00875)
Type
Small Molecule
Groups
Approved, Investigational
Description

An ethanolamine-derivative, first generation histamine H1 antagonist used in hay fever, rhinitis, allergic skin conditions, and pruritus. It causes drowsiness.

Structure
Thumb
Synonyms
  • (+)-(2R)-2-(2-(((R)-p-chloro-α-methyl-α-phenylbenzyl)oxy)ethyl)-1-methylpyrrolidine
  • (+)-(2R)-2-[2-[[(R)-p-chloro-α-methyl-α-phenylbenzyl]oxy]ethyl]-1-methylpyrrolidine
  • Clemastina
  • Clemastinum
  • Meclastin
External IDs
HS-592
Product Ingredients
IngredientUNIICASInChI Key
Clemastine fumarate19259EGQ3D14976-57-9PMGQWSIVQFOFOQ-YKVZVUFRSA-N
Product Images
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Clemastine FumarateSyrup0.5 mg/5mLOralTeva1995-03-292015-09-30Us
Clemastine FumarateTablet2.68 mg/1OralPhysicians Total Care, Inc.2006-05-182011-06-30Us
Clemastine FumarateSyrup0.5 mg/1mLOralQualitest1997-12-172012-02-22Us
Clemastine FumarateTablet2.68 mg/1OralNorthwind Pharmaceuticals2014-04-28Not applicableUs00093 0308 01 nlmimage10 342b1a18
Clemastine FumarateTablet2.68 mg/1OralTeva Pharmaceuticals USA, Inc.1992-04-01Not applicableUs0093 030820180814 13942 13ntjuc
Clemastine FumarateTablet2.68 mg/1OralSandoz1993-10-312016-10-31Us
Clemastine FumarateTablet2.68 mg/1OralNorthwind Pharmaceuticals2014-04-282014-06-25Us
Clemastine FumarateSyrup0.67 mg/5mLOralLannett Company, Inc.1997-12-17Not applicableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Allergy ReliefTablet1.34 mg/1OralCVS Health1996-08-282014-03-21Us
Clemastine FumarateTablet1.34 mg/1OralCarilion Materials Management1993-10-31Not applicableUs
Clemastine FumarateTablet1.34 mg/1OralPhysicians Total Care, Inc.2008-06-27Not applicableUs
Clemastine FumarateTablet1.34 mg/1OralSandoz1993-10-312016-10-31Us
Dayhist AllergyTablet1.34 mg/1OralH.E.B.1995-08-302016-12-16Us
Dayhist allergyTablet1.34 mg/1OralHyvee1996-06-21Not applicableUs
Dayhist AllergyTablet1.34 mg/1OralPublix Supermarkets, Inc.1996-11-202018-10-24Us
Dayhist Allergy 12 Hour ReliefTablet1.34 mg/1OralKroger1996-08-072014-08-13Us
Good Neighbor Pharmacy Dayhist AllergyTablet1.34 mg/1OralAmerisource Bergen1996-06-28Not applicableUs
Good Sense dayhist allergyTablet1.34 mg/1OralL. Perrigo Company1996-07-112011-04-06Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Tavist-D TabletsClemastine (1 mg) + Phenylpropanolamine hydrochloride (75 mg)Tablet, extended releaseOralNovartis1992-12-312001-04-24Canada
International/Other Brands
Agasten (Novartis (Brazil)) / Allerhist-1 / Tavegil (Novartis) / Tavegyl (Novartis) / Tavist (Novartis) / Tavist-1 (Novartis)
Categories
UNII
95QN29S1ID
CAS number
15686-51-8
Weight
Average: 343.89
Monoisotopic: 343.170292166
Chemical Formula
C21H26ClNO
InChI Key
YNNUSGIPVFPVBX-NHCUHLMSSA-N
InChI
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
IUPAC Name
(2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine
SMILES
CN1CCC[C@@H]1CCO[C@](C)(C1=CC=CC=C1)C1=CC=C(Cl)C=C1

Pharmacology

Indication

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.

Associated Conditions
Pharmacodynamics

Clemastine is an antihistamine with anticholinergic (drying) and sedative side effects. Antihistamines competitively antagonize various physiological effects of histamine including increased capillary permeability and dilatation, the formation of edema, the "flare" and "itch" response, and gastrointestinal and respiratory smooth muscle constriction. Within the vascular tree, H1- receptor antagonists inhibit both the vasoconstrictor and vasodilator effects of histamine. Depending on the dose, H1- receptor antagonists can produce CNS stimulation or depression. Most antihistamines exhibit central and/or peripheral anticholinergic activity. Antihistamines act by competitively blocking H1- receptor sites. Antihistamines do not pharmacologically antagonize or chemically inactivate histamine, nor do they prevent the release of histamine.

Mechanism of action

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.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Rapidly absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Antihistamines appear to be metabolized in the liver chiefly via mono- and didemethylation and glucuronide conjugation.

Route of elimination

Urinary excretion is the major mode of elimination.

Half life
Not Available
Clearance
Not Available
Toxicity

Oral LD50 in rat and mouse is 3550 mg/kg and 730 mg/kg, respectively. Antihistamine overdosage reactions may vary from central nervous system depression to stimulation. In children, stimulation predominates initially in a syndrome which may include excitement, hallucinations, ataxia, incoordination, muscle twitching, athetosis, hyperthermia, cyanosis convulsions, tremors, and hyperreflexia followed by postictal depression and cardio-respiratory arrest. Convulsions in children may be preceded by mild depression. Dry mouth, fixed dilated pupils, flushing of the face, and fever are common. In adults, CNS depression, ranging from drowsiness to coma, is more common.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Clemastine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Clemastine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Clemastine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Clemastine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Clemastine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Clemastine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Clemastine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Clemastine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Clemastine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbexinostatThe risk or severity of QTc prolongation can be increased when Abexinostat is combined with Clemastine.
AcebutololThe risk or severity of QTc prolongation can be increased when Acebutolol is combined with Clemastine.
Food Interactions
  • Avoid alcohol.
  • Take with food.

References

Synthesis Reference

British Patent 942,152; November 20,1963; assigned to Sandoz Ltd.

General References
  1. Hayashi H, Okajima M, Yamada K: Atrial T (Ta) loop in dogs with or without atrial injury. Am Heart J. 1976 May;91(5):607-17. [PubMed:1266718]
  2. Schran HF, Petryk L, Chang CT, O'Connor R, Gelbert MB: The pharmacokinetics and bioavailability of clemastine and phenylpropanolamine in single-component and combination formulations. J Clin Pharmacol. 1996 Oct;36(10):911-22. [PubMed:8930778]
External Links
Human Metabolome Database
HMDB0014428
KEGG Drug
D03535
KEGG Compound
C06913
PubChem Compound
26987
PubChem Substance
46506492
ChemSpider
25129
BindingDB
50253157
ChEBI
3738
ChEMBL
CHEMBL1626
Therapeutic Targets Database
DAP000322
PharmGKB
PA164776997
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Clemastine
ATC Codes
D04AA14 — ClemastineR06AA04 — ClemastineR06AA54 — Clemastine, combinations
MSDS
Download (74.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticHealthy Volunteers1
1CompletedTreatmentAllergies1
2CompletedTreatmentChronic Urticaria1
2CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
2RecruitingTreatmentOptic Neuritis1
3Unknown StatusTreatmentAllergies / Skin Inflammation1

Pharmacoeconomics

Manufacturers
  • Actavis mid atlantic llc
  • Novex pharma
  • Silarx pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Teva pharmaceuticals usa
  • Wockhardt eu operations (swiss) ag
  • Novartis pharmaceuticals corp
  • Perrigo co
  • Sandoz inc
Packagers
  • Apotex Inc.
  • Boca Pharmacal
  • CVS Pharmacy
  • Dispensing Solutions
  • H.J. Harkins Co. Inc.
  • Kroger Co.
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Novartis AG
  • Novex Pharma
  • Nucare Pharmaceuticals Inc.
  • Perrigo Co.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Prescript Pharmaceuticals
  • Professional Co.
  • Qualitest
  • Sandoz
  • Silarx Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • United Research Laboratories Inc.
  • Wockhardt Ltd.
Dosage forms
FormRouteStrength
SyrupOral0.5 mg/5mL
SyrupOral0.5 mg/1mL
SyrupOral0.67 mg/5mL
TabletOral2.68 mg/1
TabletOral1.34 mg/1
SyrupOral0.5 mg
TabletOral1 mg
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
Clemastine fumarate powder255.0USD g
Clemastine Fumarate 0.67 mg/5ml Syrup 120ml Bottle22.2USD bottle
Clemastine Fumarate 2.68 mg tablet0.9USD tablet
Clemastine fum 2.68 mg tablet0.86USD tablet
Tavist nd 10 mg tablet0.74USD tablet
Clemastine fum 1.34 mg tablet0.58USD tablet
Tavist-1 1.34 mg tablet0.5USD tablet
Clemastine Fumarate 1.34 mg tablet0.34USD tablet
Dayhist tablet0.31USD tablet
CVS Pharmacy dayhist allergy tablet0.28USD tablet
Dayhist-1 1.34 mg tablet0.25USD tablet
Tavist max-str sinus caplet0.17USD caplet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)178 °C (hydrogen fumarate formulation)Not Available
water solubilitySoluble (hydrogen fumarate formulation)Not Available
logP5.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000405 mg/mLALOGPS
logP5.29ALOGPS
logP4.92ChemAxon
logS-5.9ALOGPS
pKa (Strongest Basic)9.55ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity101.65 m3·mol-1ChemAxon
Polarizability39.06 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9942
Blood Brain Barrier+0.9918
Caco-2 permeable+0.6652
P-glycoprotein substrateSubstrate0.6659
P-glycoprotein inhibitor IInhibitor0.808
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterInhibitor0.8471
CYP450 2C9 substrateNon-substrate0.819
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7176
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorInhibitor0.8993
CYP450 3A4 inhibitorInhibitor0.7028
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5
Ames testNon AMES toxic0.7454
CarcinogenicityNon-carcinogens0.8549
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.9450 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5986
hERG inhibition (predictor II)Inhibitor0.8702
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Benzylethers / Chlorobenzenes / N-alkylpyrrolidines / Aryl chlorides / Trialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Diphenylmethane / Benzylether / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / N-alkylpyrrolidine / Pyrrolidine / Tertiary aliphatic amine / Tertiary amine
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monochlorobenzenes, N-alkylpyrrolidine (CHEBI:3738)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Taniguchi K, Urakami M, Takanaka K: [Effects of antiallergic agents on polymorphonuclear leukocytes. The inhibition of arachidonic acid release and superoxide production]. Nihon Yakurigaku Zasshi. 1987 Aug;90(2):97-103. [PubMed:2890562]
  3. Hallberg T, Dohlsten M, Baldetorp B: Demonstration of histamine receptors on human platelets by flow cytometry. Scand J Haematol. 1984 Feb;32(2):113-8. [PubMed:6701456]
  4. Dorsch W, Hintschich C, Neuhauser J, Weber J: Sequential histamine inhalations cause increased bronchial histamine reactivity in guinea pigs: role of platelets, thromboxanes and prostacyclin. Naunyn Schmiedebergs Arch Pharmacol. 1984 Sep;327(2):148-55. [PubMed:6387510]
  5. Taniguchi K, Masuda Y, Takanaka K: Inhibitory effects of histamine H1 receptor blocking drugs on metabolic activations of neutrophils. J Pharmacobiodyn. 1991 Feb;14(2):87-93. [PubMed:1678430]
  6. Oishi R, Shishido S, Yamori M, Saeki K: Comparison of the effects of eleven histamine H1-receptor antagonists on monoamine turnover in the mouse brain. Naunyn Schmiedebergs Arch Pharmacol. 1994 Feb;349(2):140-4. [PubMed:7513381]
  7. Thomas RH, Browne PD, Kirby JD: The influence of ranitidine, alone and in combination with clemastine, on histamine-mediated cutaneous weal and flare reactions in human skin. Br J Clin Pharmacol. 1985 Oct;20(4):377-82. [PubMed:4074605]
  8. Thomson NC, Kerr JW: Effect of inhaled H1 and H2 receptor antagonist in normal and asthmatic subjects. Thorax. 1980 Jun;35(6):428-34. [PubMed:6449094]
  9. Hayashi H, Okajima M, Yamada K: Atrial T (Ta) loop in dogs with or without atrial injury. Am Heart J. 1976 May;91(5):607-17. [PubMed:1266718]
  10. Schran HF, Petryk L, Chang CT, O'Connor R, Gelbert MB: The pharmacokinetics and bioavailability of clemastine and phenylpropanolamine in single-component and combination formulations. J Clin Pharmacol. 1996 Oct;36(10):911-22. [PubMed:8930778]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:43