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Identification
NameClemastine
Accession NumberDB00283  (APRD00875)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
Synonyms
(+)-(2R)-2-(2-(((R)-P-chloro-alpha-Methyl-alpha-phenylbenzyl)oxy)ethyl)-1-methylpyrrolidine
(+)-(2R)-2-[2-[[(R)-P-chloro-alpha-Methyl-alpha-phenylbenzyl]oxy]ethyl]-1-methylpyrrolidine
Clemastina
Clemastine
Clemastinum
Meclastin
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Clemastine Fumaratetablet2.68 mg/1oralTeva Pharmaceuticals USA Inc1992-04-01Not applicableUs
Clemastine Fumaratesyrup.5 mg/mLoralSilarx Pharmaceuticals, Inc1997-12-17Not applicableUs
Clemastine Fumaratetablet2.68 mg/1oralNorthwind Pharmaceuticals, LLC2014-04-28Not applicableUs
Clemastine Fumaratetablet2.68 mg/1oralSandoz Inc1993-10-31Not applicableUs
Clemastine Fumaratesyrup.5 mg/mLoralQualitest Pharmaceuticals, Inc1997-12-17Not applicableUs
Approved Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Allergy Relieftablet1.34 mg/1oralCVS Pharmacy1996-08-28Not applicableUs
Clemastine Fumaratetablet1.34 mg/1oralSandoz Inc1993-10-312016-10-31Us
Clemastine Fumaratetablet1.34 mg/1oralCarilion Materials Management1993-10-31Not applicableUs
Clemastine Fumaratetablet1.34 mg/1oralPhysicians Total Care, Inc.2008-06-27Not applicableUs
Dayhist Allergytablet1.34 mg/1oralH E B1995-08-30Not applicableUs
Dayhist Allergytablet1.34 mg/1oralPublix Super Markets Inc1996-11-20Not applicableUs
Dayhist Allergytablet1.34 mg/1oralHy Vee Inc1996-06-21Not applicableUs
Dayhist Allergy 12 Hour Relieftablet1.34 mg/1oralKroger Company1996-08-07Not applicableUs
Good Neighbor Pharmacy Dayhist Allergytablet1.34 mg/1oralAmerisource Bergen1996-06-28Not applicableUs
Good Sense Dayhist Allergytablet1.34 mg/1oralL Perrigo Company1996-07-11Not applicableUs
Leader Allerhisttablet1.34 mg/1oralCardinal Health1997-09-30Not applicableUs
Sunmark 12 Hour Allergy Relieftablet1.34 mg/1oralMc Kesson2003-07-03Not applicableUs
Tavist Allergytablet1.34 mg/1oralNovartis Consumer Health, Inc.2010-01-01Not applicableUs
Tavist Tablets 1mgtablet1 mgoralNovartis Consumer Health Canada Inc.1997-05-202014-07-23Canada
Topcare Dayhist Allergytablet1.34 mg/1oralTopco Associates LLC1996-07-23Not applicableUs
Wal Histtablet1.34 mg/1oralWalgreen Company1996-05-31Not applicableUs
Wal Hist 12 Hour Relieftablet1.34 mg/1oralWalgreen Company1996-05-31Not applicableUs
Unapproved/Other Products Not Available
International Brands
NameCompany
AgastenNovartis (Brazil)
Allerhist-1Not Available
TavegilNovartis
TavegylNovartis
TavistNovartis
Tavist-1Novartis
Brand mixtures
NameLabellerIngredients
Tavist-D TabletsNovartis Consumer Health Canada Inc.
Salts
Name/CASStructureProperties
Clemastine fumarate
ThumbNot applicableDBSALT000901
Categories
UNII95QN29S1ID
CAS number15686-51-8
WeightAverage: 343.89
Monoisotopic: 343.170292166
Chemical FormulaC21H26ClNO
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Benzylether
  • Halobenzene
  • Chlorobenzene
  • N-alkylpyrrolidine
  • Aryl halide
  • Aryl chloride
  • Pyrrolidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsClemastine 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 actionClemastine 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.
Related Articles
AbsorptionRapidly absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

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

Route of eliminationUrinary excretion is the major mode of elimination.
Half lifeNot Available
ClearanceNot Available
ToxicityOral 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
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
Dosage forms
FormRouteStrength
Syruporal.5 mg/mL
Tabletoral2.68 mg/1
Tabletoral1.34 mg/1
Tabletoral1 mg
Tablet (extended-release)oral
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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point178 °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
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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
ATC CodesD04AA14R06AA04R06AA54
AHFS Codes
  • 04:04.04
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (74.2 KB)
Interactions
Drug Interactions
Drug
AclidiniumAclidinium may increase the anticholinergic activities of Clemastine.
AmphetamineAmphetamine may decrease the sedative activities of Clemastine.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Clemastine.
AzelastineClemastine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Clemastine.
Benzylpenicilloyl PolylysineClemastine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Clemastine.
Botulinum Toxin Type AClemastine may increase the anticholinergic activities of Botulinum Toxin Type A.
Botulinum Toxin Type BClemastine may increase the anticholinergic activities of Botulinum Toxin Type B.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
BuprenorphineClemastine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
CathinoneCathinone may decrease the sedative activities of Clemastine.
Cimetropium BromideClemastine may increase the anticholinergic activities of Cimetropium Bromide.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
EluxadolineClemastine may increase the activities of Eluxadoline.
EthanolClemastine may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
Glucagon recombinantThe risk or severity of adverse effects can be increased when Clemastine is combined with Glucagon recombinant.
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Clemastine.
HydrocodoneClemastine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
Ipratropium bromideIpratropium bromide may increase the anticholinergic activities of Clemastine.
IsocarboxazidIsocarboxazid may increase the anticholinergic activities of Clemastine.
ItoprideThe therapeutic efficacy of Itopride can be decreased when used in combination with Clemastine.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Clemastine.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
MethotrimeprazineClemastine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
MetyrosineClemastine may increase the sedative activities of Metyrosine.
MianserinMianserin may increase the anticholinergic activities of Clemastine.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
MirabegronThe risk or severity of adverse effects can be increased when Clemastine is combined with Mirabegron.
MirtazapineClemastine may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
MoclobemideMoclobemide may increase the anticholinergic activities of Clemastine.
MorphineThe risk or severity of adverse effects can be increased when Clemastine is combined with Morphine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
OrphenadrineClemastine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
ParaldehydeClemastine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineThe risk or severity of adverse effects can be increased when Clemastine is combined with Paroxetine.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
PhenelzinePhenelzine may increase the anticholinergic activities of Clemastine.
Potassium ChlorideClemastine may increase the ulcerogenic activities of Potassium Chloride.
PramipexoleClemastine may increase the sedative activities of Pramipexole.
PramlintidePramlintide may increase the anticholinergic activities of Clemastine.
ProcyclidineThe risk or severity of adverse effects can be increased when Procyclidine is combined with Clemastine.
RamosetronClemastine may increase the activities of Ramosetron.
RopiniroleClemastine may increase the sedative activities of Ropinirole.
RotigotineClemastine may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Clemastine.
SecretinThe therapeutic efficacy of Secretin can be decreased when used in combination with Clemastine.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
SulpirideThe therapeutic efficacy of Sulpiride can be decreased when used in combination with Clemastine.
SuvorexantClemastine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TacrineThe therapeutic efficacy of Clemastine can be decreased when used in combination with Tacrine.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Clemastine.
ThalidomideClemastine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
TiotropiumClemastine may increase the anticholinergic activities of Tiotropium.
TopiramateThe risk or severity of adverse effects can be increased when Clemastine is combined with Topiramate.
TranylcypromineTranylcypromine may increase the anticholinergic activities of Clemastine.
TrichlormethiazideThe serum concentration of Trichlormethiazide can be increased when it is combined with Clemastine.
UmeclidiniumUmeclidinium may increase the anticholinergic activities of Clemastine.
ZolpidemClemastine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food Interactions
  • Avoid alcohol.
  • Take with food.

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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
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]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 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 ]
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Drug created on June 13, 2005 07:24 / Updated on April 04, 2014 14:33