azelastine hydrochloride

Names

[ Name ]:
azelastine hydrochloride

[Synonym ]:
Azelastine hydrochloride
1(2H)-Phthalazinone, 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-, hydrochloride (1:1)
4-((4-Chlorophenyl)methyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthalazinone hydrochloride
4-((4-Chlorophenyl)methyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)phthalazin-1(2H)-one hydrochloride
UNII:0L591QR10I
1(2H)-phthalazinone, 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-, monohydrochloride
4-(4-Chlorobenzyl)-2-(1-methyl-4-azepanyl)-1(2H)-phthalazinone hydrochloride (1:1)
4-(4-chlorobenzyl)-2-(1-methylazepan-4-yl)phthalazin-1(2H)-one hydrochloride
azelastinum [INN_la]
4-(4-Chlorobenzyl)-2-(1-methylazepan-4-yl)phthalazin-1(2H)-one hydrochloride (1:1)
MFCD00242783
4-(4-Chlorbenzyl)-2-(1-methylazepan-4-yl)phthalazin-1(2H)-onhydrochlorid
4-(4-chlorobenzyl)-2-(1-méthylazépan-4-yl)phtalazin-1(2H)-one chlorhydrate
Azelastine (hydrochloride)

Biological Activity

[Description]:

Azelastine HCl is a potent, second-generation, selective, histamine antagonist.Target: Histamine ReceptorAzelastine is a selective H(1)-receptor antagonist that inhibits histamine release and interferes with activation of several other mediators of allergic inflammation. Azelastine can inhibit CHMCs activation and release of IL-6, tryptase, and histamine. On an equimolar basis, azelastine was a more potent inhibitor than olopatadine [1]. Topical azelastine progressively improved itching and conjunctival redness in PAC patients compared to placebo and was at least as effective as levocabastine. Rapid relief is consistent with H(1)-receptor antagonist action, while continued improvement up to 6 weeks may be consistent with mechanisms involving other mediators of allergic inflammation [2]. Azelastine nasal spray was reported to control all rhinitis symptoms, including nasal congestion, regardless of rhinitis diagnosis during the 2-week study period. Patients with seasonal allergic rhinitis and patients with seasonal allergic rhinitis plus nonallergic triggers were identified as patient types most likely to respond to azelastine nasal spray [3].

[Related Catalog]:

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

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Inflammation/Immunology

[References]

[1]. Kempuraj, D., et al., Azelastine is more potent than olopatadine n inhibiting interleukin-6 and tryptase release from human umbilical cord blood-derived cultured mast cells. Ann Allergy Asthma Immunol, 2002. 88(5): p. 501-6.

[2]. Canonica, G.W., et al., Topical azelastine in perennial allergic conjunctivitis. Curr Med Res Opin, 2003. 19(4): p. 321-9.

[3]. Lieberman, P., M.A. Kaliner, and W.J. Wheeler, Open-label evaluation of azelastine nasal spray in patients with seasonal allergic rhinitis and nonallergic vasomotor rhinitis. Curr Med Res Opin, 2005. 21(4): p. 611-8.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.25 g/cm3

[ Boiling Point ]:
533.9ºC at 760 mmHg

[ Melting Point ]:
225-229ºC

[ Molecular Formula ]:
C₂₂H₂₅Cl₂N₃O

[ Molecular Weight ]:
418.359

[ Flash Point ]:
276.7ºC

[ Exact Mass ]:
417.137482

[ PSA ]:
38.13000

[ LogP ]:
5.03740

[ Stability ]:
Incompatible with strong oxidizing agents.

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TH9203900

CHEMICAL NAME :: 1(2H)-Phthalazinone, 4-((4-chlorophenyl)methyl)-2-(hexahydro-1-methyl-1H-a zepin-4-yl)-, monohydrochloride

CAS REGISTRY NUMBER :: 79307-93-0

LAST UPDATED :: 199206

DATA ITEMS CITED :: 21

MOLECULAR FORMULA :: C22-H24-Cl-N3-O.Cl-H

MOLECULAR WEIGHT :: 418.40

WISWESSER LINE NOTATION :: T66 BVNNJ E1R DG& C- DT7NTJ A1 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 580 mg/kg

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

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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 80500 ug/kg

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

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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 24600 ug/kg

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

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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 115 mg/kg

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

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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 143 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands

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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 59600 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands

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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 25400 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands

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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 57200 ug/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) 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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 107 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Gastrointestinal - nausea or vomiting

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: 20,5235,1986

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 126 mg/kg

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

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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 37300 ug/kg

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

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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 23 mg/kg

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

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: 20,5231,1986

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

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 46200 ug/kg

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

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: 20,5231,1986 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1050 mg/kg/5W-C

TOXIC EFFECTS :: Liver - changes in liver weight Kidney, Ureter, Bladder - urine volume increased Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

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: 20,5238,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 5460 mg/kg/26W-C

TOXIC EFFECTS :: Liver - changes in liver weight Kidney, Ureter, Bladder - urine volume increased

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: 20,5273,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 10920 mg/kg/52W-C

TOXIC EFFECTS :: Liver - changes in liver weight Kidney, Ureter, Bladder - other changes in urine composition Kidney, Ureter, Bladder - changes in bladder weight

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: 20,5287,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 700 mg/kg/5W-C

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Related to Chronic Data - death

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: 20,5251,1986 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6729 mg/kg

SEX/DURATION :: male 11 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - other measures of fertility

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1225,1981

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 330 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1225,1981

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 755 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1225,1981

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 390 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - abortion Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1225,1981

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Precautionary Statements ]:
P301 + P312 + P330

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
22

[ RIDADR ]:
NONH for all modes of transport

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