KETOTIFEN FUMARATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H19NOS.C4H4O4
Molecular Weight	425.497
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

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

InChI

InChIKey=YNQQEYBLVYAWNX-WLHGVMLRSA-N

InChI=1S/C19H19NOS.C4H4O4/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;5-3(6)1-2-4(7)8/h2-5,8,11H,6-7,9-10,12H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1+

HIDE SMILES / InChI

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C19H19NOS
Molecular Weight	309.425
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 7 2	Inhibitor 8,297
Histamine H1 receptor 315	Antagonist 2,778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic conjunctivitis 100	Palliative		Approved 8,429	ALAWAY

C_max

Value	Dose	Co-administered	Analyte	Population
281 pg/mL	2 mg single, oral		KETOTIFEN plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
4703 pg × h/mL	2 mg single, oral		KETOTIFEN plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.1 h	2 mg single, oral		KETOTIFEN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
25%			KETOTIFEN plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
120 mg single, oral Overdose	unhealthy, 21 years n = 1	Other AEs: Abdominal pain, Headache...
1.5 mg 1 times / day multiple, oral Overdose	unhealthy, 4 months n = 1	Disc. AE: Irritability, Drowsiness...
0.05 mg/mL 1 times / day multiple, ophthalmic	unhealthy, 69 years n = 1	Disc. AE: Allergic contact dermatitis...
2 mg 2 times / day multiple, oral Highest studied dose	unhealthy, adult n = 1

Showing 1 to 4 of 4 entries

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AEs

Show entries

AE	Significance	Dose	Population
Headache	1 patient	120 mg single, oral Overdose	unhealthy, 21 years n = 1
Abdominal pain	mild, 1 patient	120 mg single, oral Overdose	unhealthy, 21 years n = 1
Drowsiness	1 patient Disc. AE	1.5 mg 1 times / day multiple, oral Overdose	unhealthy, 4 months n = 1
Encephalopathy toxic	1 patient Disc. AE	1.5 mg 1 times / day multiple, oral Overdose	unhealthy, 4 months n = 1
Irritability	1 patient Disc. AE	1.5 mg 1 times / day multiple, oral Overdose	unhealthy, 4 months n = 1

Showing 1 to 5 of 6 entries

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Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:92511	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:92511
ChemicalBook	CB9249738	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9249738
MolPort	MolPort-001-933-278	https://www.molport.com/shop/molecule-link/MolPort-001-933-278
ZINC	ZINC000000004351	http://zinc15.docking.org/substances/ZINC000000004351
eMolecules	626322	https://www.emolecules.com/cgi-bin/more?vid=626322

Showing 1 to 5 of 5 entries

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PubMed

Show entries

Title	Date	PubMed
A new model of allergic rhinitis in rats by topical sensitization and evaluation of H(1)-receptor antagonists.	2000 Jun	10822083
Impact of rhinitis on airway inflammation: biological and therapeutic implications.	2001	11737929
Role of histamine in aggravation of gastric acid back-diffusion and vascular permeability in septic rats.	2001 Dec 31	11908549
Influence of chronic treatment with H1 receptor antagonists on the anticonvulsant activity of antiepileptic drugs.	2001 Jan-Feb	11785920
Effect of bile salts on colonic mucus secretion in isolated vascularly perfused rat colon.	2001 Jun	11414298

Showing 1 to 5 of 24 entries

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Patents

Sample Use Guides

In Vivo Use Guide

1 drop in the affected eye twice daily, every 8-12 hours, not more than twice per day

Route of Administration: Other

In Vitro Use Guide

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).