Ketotifen fumarate

Names

[ Name ]:
Ketotifen fumarate

[Synonym ]:
Ketotifen hydrogen fumarate
Zaditor
4-(1-methylpiperidin-4-ylidene)-4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one (2E)-but-2-enedioate
acide (2E)-but-2-ènedioïque - 4-(1-méthylpipéridin-4-ylidène)-4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophén-10-one (1:1)
Ketotifen fumarate
4-(1-Methylpiperidin-4-ylidene)-4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one (2E)-but-2-enedioate (1:1)
UNII:HBD503WORO
Ketotifen fumarate salt
Alaway
10H-Benzo[4,5]cyclohepta[1,2-b]thiophen-10-one, 4,9-dihydro-4-(1-methyl-4-piperidinylidene)-, (2E)-2-butenedioate (1:1)
(2E)-But-2-endisäure--4-(1-methylpiperidin-4-yliden)-4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-on(1:1)
Zaditen
UNII-HBD503WORO
MFCD00079394
4-(1-Methyl-4-piperidinylidene)-4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one (2E)-2-butenedioate (1:1)
EINECS 252-100-0
Ketotifen (fumarate)

Biological Activity

[Description]:

Ketotifen (fumarate) is a second-generation noncompetitive H1-antihistamine and mast cell stabilizer, which is used to prevent asthma attacks.Target: Histamine Receptor Ketotifen is a second-generation noncompetitive H1-antihistamine and mast cell stabilizer. It is most commonly sold as a salt of fumaric acid,ketotifen fumarate, and is available in two forms. In its ophthalmic form, it is used to treat allergic conjunctivitis, or the itchy red eyes caused by allergies. In its oral form, it is used to prevent asthma attacks. Side effects include drowsiness, weight gain, dry mouth, irritability, and increased nosebleeds.Ketotifen relieves and prevents eye itchiness and/or irritation associated with most seasonal allergies. It starts working within minutes after administering the drops. The drug has not been studied in children under three. The mean elimination half life is 12 hours. Besides its anti-histaminic activity, it is also a functional leukotriene antagonist and a phosphodiesterase inhibitor. The drug may also help relieve the symptoms of Irritable bowel syndrome.

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Histamine Receptor

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Inflammation/Immunology

[References]

[1]. Klooker TK, et al. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut. 2010 Sep;59(9):1213-21.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
0.968 g/mL at 25 °C(lit.)

[ Boiling Point ]:
250-263 °C(lit.)

[ Melting Point ]:
-43°C

[ Molecular Formula ]:
C₂₃H₂₃NO₅S

[ Molecular Weight ]:
425.497

[ Flash Point ]:
96-98°C/5mm

[ Exact Mass ]:
425.129700

[ PSA ]:
123.15000

[ LogP ]:
3.66410

[ Index of Refraction ]:
n20/D 1.522(lit.)

[ Storage condition ]:
Store at RT

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DE8260000

CAS REGISTRY NUMBER :: 34580-14-8

LAST UPDATED :: 199409

DATA ITEMS CITED :: 14

MOLECULAR FORMULA :: C19-H19-N-O-S.C4-H4-O4

MOLECULAR WEIGHT :: 425.53

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 500 ug/kg

TOXIC EFFECTS :: Behavioral - general anesthetic Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: DRSAEA Drug Safety. (Adis International Ltd., Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand) V.5- 1990- Volume(issue)/page/year: 7,387,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 286 ug/kg

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions Cardiac - pulse rate

REFERENCE :: DRSAEA Drug Safety. (Adis International Ltd., Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand) V.5- 1990- Volume(issue)/page/year: 7,387,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 200 ug/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - respiratory stimulation Nutritional and Gross Metabolic - body temperature increase

REFERENCE :: DRSAEA Drug Safety. (Adis International Ltd., Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand) V.5- 1990- Volume(issue)/page/year: 7,387,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 500 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity)

REFERENCE :: DRSAEA Drug Safety. (Adis International Ltd., Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand) V.5- 1990- Volume(issue)/page/year: 7,387,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 500 ug/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified Cardiac - pulse rate increase, without fall in BP Lungs, Thorax, or Respiration - respiratory stimulation

REFERENCE :: DRSAEA Drug Safety. (Adis International Ltd., Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand) V.5- 1990- Volume(issue)/page/year: 7,387,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 1 mg/kg

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - cyanosis

REFERENCE :: DRSAEA Drug Safety. (Adis International Ltd., Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand) V.5- 1990- Volume(issue)/page/year: 7,387,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 360 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 13,4069,1979

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 370 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - chromodacryorrhea Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 13,4069,1979

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 5100 ug/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 13,4069,1979

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 585 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 13,4069,1979

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 820 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Blood - changes in spleen

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 13,4069,1979

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 18800 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 13,4069,1979 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4500 mg/kg/5W-I

TOXIC EFFECTS :: Liver - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 13,4069,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4680 mg/kg/26W-I

TOXIC EFFECTS :: Liver - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 13,4069,1979

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Precautionary Statements ]:
P301 + P312 + P330

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Faceshields;Gloves

[ Hazard Codes ]:
Xn:Harmful

[ Risk Phrases ]:
R22

[ Safety Phrases ]:
S36

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
DE8260000

[ HS Code ]:
2934999090

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Development and validation of an ultra-performance liquid chromatography method for simultaneous analysis of 20 antihistaminics in dietary supplements.

Biomed. Chromatogr. 29(3) , 465-74, (2015)

The purpose of this study was to develop and validate an ultra-performance liquid chromatography method for simultaneous analysis of 20 antihistamines (illegal additives) in dietary supplements. The l...

[Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options].

Dtsch. Med. Wochenschr. 139(30) , 1523-34; quiz 1535-8, (2014)

In the present paper clinical phenotypes, pathogenetic relationships, and diagnostic algorithms as well as therapeutic concepts of/for systemic mast cell activation disease are reviewed. The reader sh...

The effect of antihistamines on seizures induced by increasing-current electroshocks: ketotifen, but not olopatadine, promotes the seizures in infant rats.

Biol. Pharm. Bull. 35(5) , 693-7, (2012)

Clinical reports have shown that some antihistamines, such as ketotifen, occasionally produced seizures, especially in pre-school age children or young patients with epilepsy. The purpose of this stud...