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.

Structure

Similar Structures

Synonyms

Ketotifen
Ketotifene
Ketotifeno
Ketotifenum

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Ketotifen fumarate	HBD503WORO	34580-14-8	YNQQEYBLVYAWNX-WLHGVMLRSA-N

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Ketotifen Ophthalmic Solution	Solution		Ophthalmic	Sterimax Inc	2013-03-07	Not applicable
Zaditen	Syrup		Oral	TEVA Canada Limited	1990-12-31	Not applicable
Zaditen	Tablet		Oral	TEVA Canada Limited	1990-12-31	Not applicable
Zaditen - Dps 1mg/ml	Solution / drops		Oral	Novartis	Not applicable	Not applicable
Zaditor	Solution	0.345 mg/1mL	Ophthalmic	Novartis Ophthalmics	1999-07-02	2008-10-31
Zaditor	Solution	0.345 mg/1mL	Ophthalmic	Physicians Total Care, Inc.	2002-11-04	2010-12-29
Zaditor	Solution		Ophthalmic	Laboratoires Thea	2000-08-01	Not applicable
Zaditor	Solution	0.25 mg	Ophthalmic	Novartis	2006-08-03	2012-01-17

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products

Name	Dosage	Route	Labeller	Marketing Start	Marketing End
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Apo-ketotifen - Syr 1mg/5ml	Syrup	Oral	Apotex Corporation	1996-11-07	2019-01-16
Jamp-ketotifen	Solution	Ophthalmic	Jamp Pharma Corporation	Not applicable	Not applicable
Novo-ketotifen - Syr 1mg/5ml	Syrup	Oral	Novopharm Limited	1995-12-31	2015-10-26
Novo-ketotifen Tab 1mg	Tablet	Oral	Novopharm Limited	1997-07-29	2013-02-11
Nu-ketotifen Syrup - 1mg/5ml	Syrup	Oral	Nu Pharm Inc	1996-12-09	2012-09-04
PMS-ketotifen	Syrup	Oral	Pharmascience Inc	1998-08-31	2013-02-07
PMS-ketotifen	Tablet	Oral	Pharmascience Inc	1998-08-31	2013-02-07

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

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Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Alaway	Solution / drops	0.25 mg/1mL	Ophthalmic	Bausch & Lomb Incorporated	2006-12-01	Not applicable
Allergy Eye	Solution / drops	0.25 mg/1mL	Ophthalmic	CVS Health	2011-01-07	2014-07-01
Allergy Eye	Solution / drops	0.25 mg/1mL	Ophthalmic	H.E.B.	2010-09-15	2015-05-01
Allergy Eye Drops	Solution / drops	0.35 mg/1mL	Ophthalmic	H.E.B.	2014-02-25	Not applicable
Allergy Eye Drops	Solution / drops	0.35 mg/1mL	Ophthalmic	Advanced Vision Research (Subsidiary of Akorn, Inc.)	2013-11-14	Not applicable
Allergy Eye Drops	Solution / drops	0.35 mg/1mL	Ophthalmic	Cardinal Health	2014-01-13	Not applicable
Allergy Eye Original Prescription Strength	Solution / drops	0.25 mg/1mL	Ophthalmic	Meijer Distribution	1995-12-12	2015-01-01
Allergy Relief Eye	Solution / drops	0.25 mg/1mL	Ophthalmic	Western Family Foods	2011-05-25	2015-06-01
Allergy Relief Eye Drops	Solution / drops	0.35 mg/1mL	Ophthalmic	Kinray	2014-03-18	Not applicable
Antihistamine Eye	Solution	0.25 mg/1mL	Ophthalmic	CVS Health	2010-10-19	2015-06-01

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Alaway	Ketotifen fumarate (0.25 mg/1mL) + Ketotifen fumarate (0.25 mg/1mL)	Kit	Ophthalmic	Bausch & Lomb Incorporated	2006-12-01	Not applicable
Alaway	Ketotifen fumarate (0.25 mg/1mL) + Ketotifen fumarate (0.25 mg/1mL)	Kit	Ophthalmic	Bausch & Lomb Incorporated	2006-12-01	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Zaditor	Ketotifen fumarate (0.345 mg/1mL)	Solution	Ophthalmic	Physicians Total Care, Inc.	2002-11-04	2010-12-29

International/Other Brands

Totifen (Patron) / Zasten (Novartis)

Categories

UNII

X49220T18G

CAS number

34580-13-7

Weight

Average: 309.425
Monoisotopic: 309.118734925

Chemical Formula

C₁₉H₁₉NOS

InChI Key

ZCVMWBYGMWKGHF-UHFFFAOYSA-N

InChI

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

IUPAC Name

2-(1-methylpiperidin-4-ylidene)-6-thiatricyclo[8.4.0.0³,⁷]tetradeca-1(14),3(7),4,10,12-pentaen-8-one

SMILES

CN1CCC(CC1)=C1C2=C(SC=C2)C(=O)CC2=CC=CC=C12

Pharmacology

Indication

Indicated as an add-on or prophylactic oral medication in the chronic treatment of mild atopic asthmatic children. Also used as self-medication for the temporary relief of itching of the eye due to allergic conjunctivitis (ophthalmic).

Associated Conditions

Pharmacodynamics

Ketotifen is a fast acting non-competitive histamine antagonist. It inhibits the release of mediators from mast cells. It is a non-bronchodilator antiasthmatic drug (when taken orally).

Mechanism of action

Ketotifen is a relatively selective, non-competitive histamine antagonist (H1-receptor) and mast cell stabilizer. 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. 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 inhibits of the release of allergic mediators such as histamine, leukotrienes C4 and D4(SRS-A) and PAF.

Target	Actions	Organism
AHistamine H1 receptor	antagonist	Humans
U6-phosphogluconate dehydrogenase, decarboxylating	inhibitor	Humans

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Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available

Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available

Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Following oral administration absorption is at least 60%

Volume of distribution

Not Available

Protein binding

75%

Metabolism

Primarily hepatic. The main metabolite found in both plasma and urine is the inactive ketotifen-N-glucuronide. Nor-ketotifen, the N-demethylated metabolite, and the 10-alpha-hydroxyl derivative are the only other metabolites detectable in human urine.

Route of elimination

Not Available

Half life

21 hours (for elimination)

Clearance

Not Available

Toxicity

Adverse reactions include headaches, conjunctival injection and rhinitis.

Affected organisms

Humans and other mammals

Pathways

Pathway	Category
Ketotifen H1-Antihistamine Action	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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2,5-Dimethoxy-4-ethylamphetamine	2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Ketotifen.
2,5-Dimethoxy-4-ethylthioamphetamine	2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Ketotifen.
4-Bromo-2,5-dimethoxyamphetamine	4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Ketotifen.
Abexinostat	The risk or severity of QTc prolongation can be increased when Ketotifen is combined with Abexinostat.
Acebutolol	The risk or severity of QTc prolongation can be increased when Ketotifen is combined with Acebutolol.
Aceprometazine	The risk or severity of QTc prolongation can be increased when Ketotifen is combined with Aceprometazine.
Acetyldigoxin	The risk or severity of QTc prolongation can be increased when Ketotifen is combined with Acetyldigoxin.
Acrivastine	The risk or severity of QTc prolongation can be increased when Ketotifen is combined with Acrivastine.
Adenosine	The risk or severity of QTc prolongation can be increased when Ketotifen is combined with Adenosine.
Ajmaline	The risk or severity of QTc prolongation can be increased when Ketotifen is combined with Ajmaline.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Take without regard to meals.

References

Synthesis Reference

Roy W. Bryant, Ravi Parihar, Thomas Rowe, Susan Caballa, "Methods of Making and Using Stable Pharmaceutical Compositions Comprising Ketotifen and Naphazoline." U.S. Patent US20110312998, issued December 22, 2011.

US20110312998

General References

Not Available

External Links

Human Metabolome Database: HMDB0015056
KEGG Drug: D01332
PubChem Compound: 3827
PubChem Substance: 46508921
ChemSpider: 3695
BindingDB: 94597
ChEBI: 92511
ChEMBL: CHEMBL534
Therapeutic Targets Database: DAP000329
PharmGKB: PA450152
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
PDRhealth: PDRhealth Drug Page
Wikipedia: Ketotifen

ATC Codes

S01GX08 — Ketotifen

R06AX17 — Ketotifen

AHFS Codes

52:02.00 — Antiallergic Agents
04:00.00 — Antihistamine Drugs
04:92.00 — Other Antihistamines

FDA label

Download (9.05 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Conjunctivitis, Seasonal Allergic	1
1, 2	Recruiting	Treatment	Widespread Chronic Pain	1
2	Completed	Treatment	Conjunctivitis, Seasonal Allergic	1
2	Unknown Status	Treatment	Peanut Allergies in Children	1
2	Withdrawn	Not Available	Conjunctivitis, Seasonal Allergic	1
3	Active Not Recruiting	Prevention	Joint Contractures	1
3	Completed	Not Available	Conjunctivitis, Seasonal Allergic	1
3	Completed	Basic Science	Fibromyalgia	1
3	Completed	Treatment	Atopic Dermatitis (AD)	1
3	Completed	Treatment	Atopics / Skin Inflammation	1
3	Completed	Treatment	Conjunctivitis, Seasonal Allergic	5
3	Completed	Treatment	Rhinitis, Allergic, Perennial	2
3	Completed	Treatment	Vernal Keratoconjunctivitis	1
3	Recruiting	Prevention	Elbow Dislocation / Elbow Fractures / Elbow Injury	1
3	Recruiting	Treatment	Functional Dyspepsia	1
4	Completed	Treatment	Asthma Bronchial	1
4	Completed	Treatment	Conjunctivitis, Seasonal Allergic	1
4	Recruiting	Treatment	Dengue Fever / Pleural Effusions	1

Pharmacoeconomics

Manufacturers

Bausch and lomb inc
Akorn inc
Alcon inc
Apotex inc etobicoke site
Novartis pharmaceuticals corp

Packagers

Akorn Inc.
Allergan Inc.
Apotex Inc.
Bausch & Lomb Inc.
Ciba Vision Canada Inc.
Novartis AG
Physicians Total Care Inc.
Spectrum Pharmaceuticals

Dosage forms

Form	Route	Strength
Kit	Ophthalmic
Solution / drops	Ophthalmic	0.35 mg/1mL
Solution	Ophthalmic	0.25 g/1mL
Solution	Ophthalmic	0.25 mg/1mL
Solution	Ophthalmic
Solution	Ophthalmic	0.35 mg/1mL
Solution / drops	Ophthalmic	0.345 mg/1mL
Syrup	Oral
Solution	Ophthalmic	.25 mg/1mL
Tablet	Oral
Solution / drops	Oral
Solution	Ophthalmic	.35 mg/1mL
Solution	Ophthalmic	0.25 mg
Solution	Ophthalmic	0.345 mg/1mL
Solution / drops	Ophthalmic	0.25 mg/1mL

Prices

Unit description	Cost	Unit
Ketotifen fumarate powder	926.63USD	g
Zaditor 0.025% Solution 5ml Bottle	74.96USD	bottle
Ketotifen fum 0.025% eye drops	2.44USD	ml
Refresh 0.025% eye drops	2.2USD	ml
Zaditor 0.025% eye drops	2.15USD	ml
Alaway 0.025% eye drops	0.96USD	ml
Zaditen 1 mg Tablet	0.83USD	tablet
Novo-Ketotifen 1 mg Tablet	0.66USD	tablet
Novo-Ketotifen 0.2 mg/ml Syrup	0.14USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	152-153	U.S. Patents 3,682,930; 3,770,728; and 3,960,894
logP	2.2	Not Available
pKa	8.43	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00787 mg/mL	ALOGPS
logP	3.49	ALOGPS
logP	3.35	ChemAxon
logS	-4.6	ALOGPS
pKa (Strongest Acidic)	12.3	ChemAxon
pKa (Strongest Basic)	7.15	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	20.31 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	101.73 m³·mol^-1	ChemAxon
Polarizability	34.61 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9923
Caco-2 permeable	+	0.8867
P-glycoprotein substrate	Substrate	0.87
P-glycoprotein inhibitor I	Inhibitor	0.8564
P-glycoprotein inhibitor II	Non-inhibitor	0.7474
Renal organic cation transporter	Inhibitor	0.8198
CYP450 2C9 substrate	Non-substrate	0.7542
CYP450 2D6 substrate	Non-substrate	0.5638
CYP450 3A4 substrate	Substrate	0.6984
CYP450 1A2 substrate	Non-inhibitor	0.9045
CYP450 2C9 inhibitor	Non-inhibitor	0.9071
CYP450 2D6 inhibitor	Inhibitor	0.8931
CYP450 2C19 inhibitor	Non-inhibitor	0.9026
CYP450 3A4 inhibitor	Non-inhibitor	0.8607
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.6414
Ames test	Non AMES toxic	0.7576
Carcinogenicity	Non-carcinogens	0.9649
Biodegradation	Not ready biodegradable	0.9547
Rat acute toxicity	2.7979 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.6336
hERG inhibition (predictor II)	Non-inhibitor	0.5145

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Taxonomy

Description: This compound belongs to the class of organic compounds known as cycloheptathiophenes. These are polycyclic compounds containing a thiophene ring fused to a 7 member carbocyclic moiety. Thiophene is 5-membered ring consisting of four carbon atoms and one sulfur atom.
Kingdom: Organic compounds
Super Class: Organoheterocyclic compounds
Class: Cycloheptathiophenes
Sub Class: Not Available
Direct Parent: Cycloheptathiophenes
Alternative Parents: Aryl alkyl ketones / Piperidines / Benzenoids / Thiophenes / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents: Cycloheptathiophene / Aryl alkyl ketone / Aryl ketone / Piperidine / Benzenoid / Thiophene / Heteroaromatic compound / Ketone / Tertiary amine / Tertiary aliphatic amine
Molecular Framework: Aromatic heteropolycyclic compounds
External Descriptors: Not Available

Targets

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	1	N/A	N/A	21470866
Ki (nM)	0.158	N/A	N/A	20942472
Ki (nM)	0.31	N/A	N/A	1350797

Details1. Histamine H1 receptor

Kind: Protein
Organism: Humans
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

Mita H, Shida T: Comparison of anti-allergic activities of the histamine H1 receptor antagonists epinastine, ketotifen and oxatomide in human leukocytes. Arzneimittelforschung. 1995 Jan;45(1):36-40. [PubMed:7893266]
Okabe S, Nakaji S, Tachibana M: Effect of ketotifen on acute gastric lesions and gastric secretion in rats. Jpn J Pharmacol. 1992 Jun;59(2):251-4. [PubMed:1434122]
Hashimoto T, Ohata H, Honda K: Lysophosphatidic acid (LPA) induces plasma exudation and histamine release in mice via LPA receptors. J Pharmacol Sci. 2006 Jan;100(1):82-7. Epub 2006 Jan 11. [PubMed:16404130]
Ito K, Sakamoto T, Hayashi Y, Morishita M, Shibata E, Sakai K, Takeuchi Y, Torii S: Role of tachykinin and bradykinin receptors and mast cells in gaseous formaldehyde-induced airway microvascular leakage in rats. Eur J Pharmacol. 1996 Jul 4;307(3):291-8. [PubMed:8836617]
Yokoyama H, Iinuma K, Yanai K, Watanabe T, Sakurai E, Onodera K: Proconvulsant effect of ketotifen, a histamine H1 antagonist, confirmed by the use of d-chlorpheniramine with monitoring electroencephalography. Methods Find Exp Clin Pharmacol. 1993 Apr;15(3):183-8. [PubMed:8101246]
Werner-Klein M, Goggel R, Westhof A, Erb KJ: Development and characterisation of a novel and rapid lung eosinophil influx model in the rat. Pulm Pharmacol Ther. 2008 Aug;21(4):648-56. doi: 10.1016/j.pupt.2008.03.002. Epub 2008 Apr 7. [PubMed:18490184]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Details2. 6-phosphogluconate dehydrogenase, decarboxylating

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Phosphogluconate dehydrogenase (decarboxylating) activity
Specific Function: Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.
Gene Name: PGD
Uniprot ID: P52209
Uniprot Name: 6-phosphogluconate dehydrogenase, decarboxylating
Molecular Weight: 53139.56 Da

References

Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Aug;25(4):476-9. doi: 10.3109/14756360903257900. [PubMed:20235752]
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on October 22, 2019 18:27

Ketotifen

Identification

Structure for Ketotifen (DB00920)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References