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Details

Stereochemistry ACHIRAL
Molecular Formula C19H19NOS
Molecular Weight 309.425
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of KETOTIFEN

SMILES

CN1CCC(CC1)=C2C3=C(SC=C3)C(=O)CC4=C2C=CC=C4

InChI

InChIKey=ZCVMWBYGMWKGHF-UHFFFAOYSA-N
InChI=1S/C19H19NOS/c1-20-9-6-13(7-10-20)18-15-5-3-2-4-14(15)12-17(21)19-16(18)8-11-22-19/h2-5,8,11H,6-7,9-10,12H2,1H3

HIDE SMILES / InChI

Molecular Formula C19H19NOS
Molecular Weight 309.425
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=24267353

Ketotifen is a cycloheptathiophene blocker of histamine H1 receptors and release of inflammatory mediators. It has been proposed for the treatment of asthma, rhinitis, skin allergies, and anaphylaxis. Ketotifen was developed in 1970 by Sandoz Pharmaceuticals of Switzerland. It is a benzocycloheptathiophene derivative and was initially marketed as an inhibitor of anaphylaxis. The pharmacodynamic properties of ketotifen are many, because it is an inhibitor of the release and/or activity of mast cell and basophil mediators, including histamine, neutrophil, and eosinophil chemotactic factors, arachidonic acid metabolites, prostaglandins, and leukotrienes. Properties of ketotifen which may contribute to its antiallergic activity and its ability to affect the underlying pathology of asthma include inhibition of the development of airway hyper-reactivity associated with activation of platelets by PAF (Platelet Activating Factor), inhibition of PAF-induced accumulation of eosinophils and platelets in the airways, suppression of the priming of eosinophils by human recombinant cytokines and antagonism of bronchoconstriction due to leukotrienes. Ketotifen is marketed under many brand names worldwide. Ketotifen inhibits the release of mediators from mast cells involved in hypersensitivity reactions. Decreased chemotaxis and activation of eosinophils have also been demonstrated. Ketotifen also inhibits cAMP phosphodiesterase.

CNS Activity

Curator's Comment: First-generation antihistamines, such as ketotifen and d-chlorpheniramine, can easily penetrate the blood–brain barrier, and tend to occupy a large proportion of postsynaptic H1Rs (>50%)

Originator

Curator's Comment: in 1970 by Sandoz Pharmaceuticals of Switzerland

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
ALAWAY

Approved Use

Uses Temporarily relieves itchy eyes due to pollen, ragweed, grass, animal hair and dander.

Launch Date

2006
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
281 pg/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
KETOTIFEN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4703 pg × h/mL
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
KETOTIFEN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.1 h
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
KETOTIFEN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
25%
KETOTIFEN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
120 mg single, oral
Overdose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
unhealthy, 21 years
n = 1
Health Status: unhealthy
Age Group: 21 years
Sex: F
Population Size: 1
Sources:
Other AEs: Abdominal pain, Headache...
Other AEs:
Abdominal pain (mild, 1 patient)
Headache (1 patient)
Sources:
1.5 mg 1 times / day multiple, oral
Overdose
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
unhealthy, 4 months
n = 1
Health Status: unhealthy
Condition: atopic dermatitis
Age Group: 4 months
Sex: M
Population Size: 1
Sources:
Disc. AE: Irritability, Drowsiness...
AEs leading to
discontinuation/dose reduction:
Irritability (1 patient)
Drowsiness (1 patient)
Encephalopathy toxic (1 patient)
Sources:
0.05 mg/mL 1 times / day multiple, ophthalmic
Dose: 0.05 mg/mL, 1 times / day
Route: ophthalmic
Route: multiple
Dose: 0.05 mg/mL, 1 times / day
Sources:
unhealthy, 69 years
n = 1
Health Status: unhealthy
Condition: seasonal allergic conjunctivitis
Age Group: 69 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Allergic contact dermatitis...
AEs leading to
discontinuation/dose reduction:
Allergic contact dermatitis (1 patient)
Sources:
2 mg 2 times / day multiple, oral
Highest studied dose
Dose: 2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2 mg, 2 times / day
Sources:
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources:
AEs

AEs

AESignificanceDosePopulation
Headache 1 patient
120 mg single, oral
Overdose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
unhealthy, 21 years
n = 1
Health Status: unhealthy
Age Group: 21 years
Sex: F
Population Size: 1
Sources:
Abdominal pain mild, 1 patient
120 mg single, oral
Overdose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
unhealthy, 21 years
n = 1
Health Status: unhealthy
Age Group: 21 years
Sex: F
Population Size: 1
Sources:
Drowsiness 1 patient
Disc. AE
1.5 mg 1 times / day multiple, oral
Overdose
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
unhealthy, 4 months
n = 1
Health Status: unhealthy
Condition: atopic dermatitis
Age Group: 4 months
Sex: M
Population Size: 1
Sources:
Encephalopathy toxic 1 patient
Disc. AE
1.5 mg 1 times / day multiple, oral
Overdose
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
unhealthy, 4 months
n = 1
Health Status: unhealthy
Condition: atopic dermatitis
Age Group: 4 months
Sex: M
Population Size: 1
Sources:
Irritability 1 patient
Disc. AE
1.5 mg 1 times / day multiple, oral
Overdose
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
unhealthy, 4 months
n = 1
Health Status: unhealthy
Condition: atopic dermatitis
Age Group: 4 months
Sex: M
Population Size: 1
Sources:
Allergic contact dermatitis 1 patient
Disc. AE
0.05 mg/mL 1 times / day multiple, ophthalmic
Dose: 0.05 mg/mL, 1 times / day
Route: ophthalmic
Route: multiple
Dose: 0.05 mg/mL, 1 times / day
Sources:
unhealthy, 69 years
n = 1
Health Status: unhealthy
Condition: seasonal allergic conjunctivitis
Age Group: 69 years
Sex: F
Population Size: 1
Sources:
PubMed

PubMed

TitleDatePubMed
Adsorption of allopurinol and ketotifen by chitosan.
2001 Jan 18
Pharmacokinetics of ketotifen fumarate after intravenous, intranasal, oral and rectal administration in rabbits.
2002 Dec
A comparison of the relative clinical efficacy of a single dose of ketotifen fumarate 0.025% ophthalmic solution versus placebo in inhibiting the signs and symptoms of allergic rhinoconjunctivitis as induced by the conjunctival allergen challenge model.
2002 Nov
[Correction with zaditen of impaired activity of pancreatic digestive enzymes in sensitization and anaphylactic shock].
2002 Sep-Oct
Determination of ketotifen and its conjugated metabolite in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study.
2003
High-frequency oscillation in the hippocampus of the behaving rat and its modulation by the histaminergic system.
2003
[In vitro effects of antiallergic eyedrops on complement activation induced by particulate matter].
2003 Apr
Effects of ketotifen 0.025% and lodoxamide 0.1% on eosinophil infiltration into the guinea pig conjunctiva in a model of allergic conjunctivitis.
2003 Apr
Role of mast cells in gastrointestinal mucosal defense.
2003 Aug
The role of platelet activating factor and the efficacy of apafant ophthalmic solution in experimental allergic conjunctivitis.
2003 Aug
[Effectiveness and impact in the quality of life of ketotifen ophthalmic solution. Results of zeta study in patients with seasonal allergic conjunctivitis].
2003 Aug
Role of mast cells and pro-inflammatory mediators on the intestinal secretion induced by cholera toxin.
2003 Aug
Evaluation of the efficacy of antihistamines using human monocyte-derived dendritic cells stimulated with histamine.
2003 Aug
Effects of TAK-427 on acute nasal symptoms and nasal obstruction in guinea pig model of experimental allergic rhinitis.
2003 Aug 29
Effects of nonsteroidal anti-inflammatory drugs on experimental allergic conjunctivitis in Guinea pigs.
2003 Dec
Interactions of olopatadine and selected antihistamines with model and natural membranes.
2003 Dec
Efficacy and safety of ketotifen fumarate 0.025% in the conjunctival antigen challenge model of ocular allergic conjunctivitis.
2003 Dec
Release of TNF-alpha during myocardial reperfusion depends on oxidative stress and is prevented by mast cell stabilizers.
2003 Dec 1
In vitro inhibition of human conjunctival mast-cell degranulation by ketotifen.
2003 Feb
Alteration of CCK-induced satiety in post-Nippostrongylus brasiliensis-infected rats.
2003 Feb
Montelukast reduces peripheral blood eosinophilia but not tissue eosinophilia or symptoms in a patient with eosinophilic gastroenteritis and esophageal stricture.
2003 Jan
The effect of ketotifen on inflammatory markers in allergic conjunctivitis: an open, uncontrolled study.
2003 Jan 6
Effects of second-generation histamine H1 receptor antagonists on the active avoidance response in rats.
2003 Jan-Feb
A placebo-controlled comparison of ketotifen fumarate and nedocromil sodium ophthalmic solutions for the prevention of ocular itching with the conjunctival allergen challenge model.
2003 Jul
Comparison of ketotifen fumarate ophthalmic solution alone, desloratadine alone, and their combination for inhibition of the signs and symptoms of seasonal allergic rhinoconjunctivitis in the conjunctival allergen challenge model: a double-masked, placebo- and active-controlled trial.
2003 Jul
Forsythia fructus inhibits the mast-cell-mediated allergic inflammatory reactions.
2003 Jun
Use of anti-asthmatic medications in elderly Taiwanese patients.
2003 Jun
Resident cardiac mast cells and ischemia-reperfusion injury.
2003 Jun
Activation of mast cells induced by agonists of proteinase-activated receptors under normal conditions and during acute inflammation in rats.
2003 Jun 20
Analysis of the spontaneous scratching behavior by NC/Nga mice: a possible approach to evaluate antipruritics for subjects with atopic dermatitis.
2003 Jun 27
A randomized comparison of chloroquine and chloroquine plus ketotifen in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children.
2003 Mar
The anti-allergic effects of a cromolyn sodium-chlorpheniramine combination compared to ketotifen in the conjunctival allergen challenge model.
2003 Mar
The use of anti-asthmatic medications among pediatric patients in Taiwan.
2003 Mar
Disposition kinetics of ketotifen from liposomal dry powder for inhalation in rat lung.
2003 Mar
Ketotifen fumarate and olopatadine hydrochloride in the treatment of allergic conjunctivitis: a real-world comparison of efficacy and ocular comfort.
2003 Mar-Apr
[Treatment of chronic idiopathic urticaria unresponsive to type 1 antihistamines in monotherapy].
2003 May
Effect of dehydroleucodine on histamine and serotonin release from mast cells in the isolated mouse jejunum.
2003 May
Inhibitory effects of ketotifen on eotaxin-dependent activation of eosinophils: consequences for allergic eye diseases.
2003 May
Efficacy of ketotifen fumarate 0.025% ophthalmic solution compared with placebo in the conjunctival allergen challenge model.
2003 May
In vitro uptake and release studies of ocular pharmaceutical agents by silicon-containing and p-HEMA hydrogel contact lens materials.
2003 May 12
Ebastine inhibits T cell migration, production of Th2-type cytokines and proinflammatory cytokines.
2003 Nov
Antiasthmatic property of polyherbal preparation E-721 B.
2003 Nov
Effect of ketotifen on the production of reactive oxygen species from human eosinophils primed by eotaxin.
2003 Nov
Epileptogenic activity induced by histamine H(1) antagonists in amygdala-kindled rats.
2003 Nov 21
Epinastine inhibits eosinophil chemotaxis and adhesion molecules in atopic dermatitis.
2003 Nov-Dec
Coincidental increase of leukotriene B4 between cerebral cortex and lung tissue of sensitized rats.
2003 Oct
Enhanced skin permeation of cationic drug ketotifen through excised guinea pig dorsal skin by surfactants with different electric charges.
2003 Oct
Efficacy and safety of ketotifen eye drops in the treatment of seasonal allergic conjunctivitis.
2003 Oct
Plasmodium falciparum gametocytaemia in Nigerian children: before, during and after treatment with antimalarial drugs.
2003 Sep
Involvement of central mu-opioid system in the scratching behavior in mice, and the suppression of it by the activation of kappa-opioid system.
2003 Sep 5
Patents

Sample Use Guides

1 drop in the affected eye twice daily, every 8-12 hours, not more than twice per day
Route of Administration: Other
Ketotifen at concentrations of approximately 10(-11) to 10(-4) M inhibited mast-cell histamine release by 90% or more. Similarly, ketotifen at approximately 10(-10) to 10(-4) M inhibited tryptase release by 90% or more (apart from a single anomalous reading).
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:25:22 GMT 2023
Edited
by admin
on Fri Dec 15 15:25:22 GMT 2023
Record UNII
X49220T18G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
KETOTIFEN
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
10-(1-methylpiperidin-4-ylidene)-5,10-dihydro-4H-benzo[5,6]cyclohepta[1,2-b]thiophen-4-one
Common Name English
KETOTIFEN [MI]
Common Name English
10H-Benzo[4,5]cyclohepta[1,2-b]thiophen-10-one, 4,9-dihydro-4-(1-methyl-4-piperidinylidene)-
Common Name English
KETOTIFEN [VANDF]
Common Name English
KETOTIFEN HYDROGEN FUMARATE IMPURITY E [EP IMPURITY]
Common Name English
Ketotifen [WHO-DD]
Common Name English
ketotifen [INN]
Common Name English
KETOTIFEN [HSDB]
Common Name English
4,9-Dihydro-4-(1-methyl-4-piperidinylidene)-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one
Common Name English
Classification Tree Code System Code
NDF-RT N0000000190
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
NCI_THESAURUS C29578
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
WHO-VATC QR06AX17
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
FDA ORPHAN DRUG 464714
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
NDF-RT N0000175519
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
WHO-ATC S01GX08
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
WHO-ATC R06AX17
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
WHO-VATC QS01GX08
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
Code System Code Type Description
CHEBI
92511
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
CAS
34580-13-7
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
EVMPD
SUB08377MIG
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
LACTMED
Ketotifen
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
WIKIPEDIA
KETOTIFEN
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
DRUG BANK
DB00920
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
MESH
D007665
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
INN
3993
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
DAILYMED
X49220T18G
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
FDA UNII
X49220T18G
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
PUBCHEM
3827
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
IUPHAR
7206
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
NCI_THESAURUS
C61799
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
ECHA (EC/EINECS)
252-099-7
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
HSDB
7283
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
ChEMBL
CHEMBL534
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
MERCK INDEX
m6624
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY Merck Index
DRUG CENTRAL
1530
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
SMS_ID
100000092111
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY
RXCUI
6146
Created by admin on Fri Dec 15 15:25:22 GMT 2023 , Edited by admin on Fri Dec 15 15:25:22 GMT 2023
PRIMARY RxNorm
Related Record Type Details
BINDER->LIGAND
BINDING
SALT/SOLVATE -> PARENT
Related Record Type Details
PARENT -> IMPURITY
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC