Azelastine
(Synonyms: 氮卓斯汀) 目录号 : GC33879
Azelastine HCl is a potent, second-generation, selective, histamine receptor antagonist, used in the treatment of rhinitis.
Cas No.:58581-89-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Azelastine HCl is a potent, second-generation, selective, histamine receptor antagonist, used in the treatment of rhinitis.
Azelastine inhibits Ag- and ionomycin-induced TNF-alpha release with IC50 values of 25.7 mM and 1.66 mM, respectively, in a rat mast RBL-2H3 cell line. Azelastine also inhibits TNF-alpha mRNA expression, TNF-alpha protein synthesis and release, and, possibly related to these effects, Ca2+ influx, in Ag-stimulated cells. Azelastine inhibits TNF-alpha release to a greater extent than mRNA expression/protein synthesis and Ca2+ influx in ionomycin-stimulated cells, suggesting that Azelastine inhibits the release process more potently than transcription or production of TNF-alpha by interfering with a signal other than Ca2+. Azelastine added 1 hour after ionomycin stimulation also immediately blocks subsequent release of TNF-alpha, which has been produced in the cells, without affecting Ca2+ influx. Azelastine inhibits ionomycin-induced, but not Ag-induced, protein kinase C translocation to the membranes. [1] Azelastine hydrochloride (Azeptin) dose-dependently suppresses both DNA and protein synthesis in human gingival fibroblasts (HF) and also suppresses blastogenesis of human peripheral blood lymphocytes (PBL). Azelastine hydrochloride (Azeptin) suppresses both inducible nitric oxide synthase-mRNA level and NO generation in mouse peritoneal macrophages. [2] Azelastine inhibits secretion of IL-6, TNF-alpha and IL-8 as well as NF-kappaB activation and intracellular calcium ion levels in normal human mast cells. [3]
[1] Hide I, et al. J Immunol,?997, 159(6), 2932-2940. [2] Yoneda K, et al. Jpn J Pharmacol,?997, 73(2), 145-153. [3] Kempuraj D, et al. Int Arch Allergy Immunol,?003, 132(3), 231-239.
| Cas No. | 58581-89-8 | SDF | |
| 别名 | 氮卓斯汀 | ||
| Canonical SMILES | O=C1N(C2CCN(C)CCC2)N=C(CC3=CC=C(Cl)C=C3)C4=C1C=CC=C4 | ||
| 分子式 | C22H24ClN3O | 分子量 | 381.9 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6185 mL | 13.0924 mL | 26.1849 mL |
| 5 mM | 0.5237 mL | 2.6185 mL | 5.237 mL |
| 10 mM | 0.2618 mL | 1.3092 mL | 2.6185 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Anti-allergic drug Azelastine suppresses colon tumorigenesis by directly targeting ARF1 to inhibit IQGAP1-ERK-Drp1-mediated mitochondrial fission
Theranostics 2021 Jan 1;11(4):1828-1844.PMID:33408784DOI:10.7150/thno.48698.
This study aimed to screen novel anticancer strategies from FDA-approved non-cancer drugs and identify potential biomarkers and therapeutic targets for colorectal cancer (CRC). Methods: A library consisting of 1056 FDA-approved drugs was screened for anticancer agents. WST-1, colony-formation, flow cytometry, and tumor xenograft assays were used to determine the anticancer effect of Azelastine. Quantitative proteomics, confocal imaging, Western blotting and JC-1 assays were performed to examine the effects on mitochondrial pathways. The target protein of Azelastine was analyzed and confirmed by DARTS, WST-1, Biacore and tumor xenograft assays. Immunohistochemistry, gain- and loss-of-function experiments, WST-1, colony-formation, immunoprecipitation, and tumor xenograft assays were used to examine the functional and clinical significance of ARF1 in colon tumorigenesis. Results: Azelastine, a current anti-allergic drug, was found to exert a significant inhibitory effect on CRC cell proliferation in vitro and in vivo, but not on ARF1-deficient or ARF1-T48S mutant cells. ARF1 was identified as a direct target of Azelastine. High ARF1 expression was associated with advanced stages and poor survival of CRC. ARF1 promoted colon tumorigenesis through its interaction with IQGAP1 and subsequent activation of ERK signaling and mitochondrial fission by enhancing the interaction of IQGAP1 with MEK and ERK. Mechanistically, Azelastine bound to Thr-48 in ARF1 and repressed its activity, decreasing Drp1 phosphorylation. This, in turn, inhibited mitochondrial fission and suppressed colon tumorigenesis by blocking IQGAP1-ERK signaling. Conclusions: This study provides the first evidence that Azelastine may be novel therapeutics for CRC treatment. ARF1 promotes colon tumorigenesis, representing a promising biomarker and therapeutic target in CRC.
Azelastine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential
Drugs 1989 Nov;38(5):778-800.PMID:2574665DOI:10.2165/00003495-198938050-00005.
Azelastine is an antiallergic agent which demonstrates histamine H1-receptor antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Azelastine antagonises histamine- and leukotriene-induced bronchospasm in animal studies and reduces airway responsiveness to inhaled antigen or distilled water, and exercise challenge. In comparative studies, orally administered Azelastine in doses up to 4 mg/day consistently relieved symptoms in patients with seasonal or perennial rhinitis - comparable to inhaled sodium cromoglycate (cromolyn sodium) 80 mg/day, oral chlorpheniramine (chlorphenamine) and oral terfenadine 120 mg/day. In addition, Azelastine administered as an intranasal spray was as effective as oral terfenadine 120 mg/day and intranasal budesonide 0.4 mg/day in alleviating symptoms of rhinitis. Azelastine is also a potent antiasthmatic agent which produces significant and long lasting bronchodilation in patients with bronchial asthma. The drug is superior to placebo and comparable to oral ketotifen 2 mg/day and sustained release theophylline 700 mg/day when administered as a twice daily oral 4 mg dose. Azelastine is generally well tolerated: the most common adverse effects are altered taste perception and drowsiness. Adverse effects are mild and transient and result in withdrawal of treatment in less than 2% of patients. In a comparative study oral Azelastine 2 or 4 mg/day produced no more sedation than terfenadine 120 mg/day. Thus, barring unexpected findings with wider clinical use, Azelastine offers an effective and well tolerated choice of treatment for patients with allergic rhinitis and/or bronchial asthma, which may be particularly beneficial in patients in whom inhaled drug treatment is contraindicated.
Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability
Curr Med Res Opin 2007 Oct;23(10):2441-52.PMID:17723160DOI:10.1185/030079907X226302.
Introduction: Azelastine hydrochloride (Astelin) nasal spray 0.1% solution is a second-generation intranasal antihistamine available in the US for treatment of both seasonal allergic rhinitis (SAR) and nonallergic vasomotor rhinitis (VMR). Scope: Searches of journal articles including the title word 'Azelastine' from 1979 through the present were conducted by the product manufacturer primarily through Medline and EMBASE but also included, at various times, Dialog, Biosis, Toxline, and Diogenes (an adverse-event database). One limitation of the present review is that it could not exclude the possibility of publication bias, whereby findings from smaller studies and/or trials with negative findings may not have been published. Findings: Azelastine is a phthalazinone derivative with H(1)-receptor binding approximately tenfold greater than chlorpheniramine on a milligram-per-milligram basis. Azelastine has demonstrated a wide range of pharmacologic effects on chemical mediators of inflammation including leukotrienes, kinins, and platelet activating factor in vitro and in vivo. The molecule also has been shown to downregulate intercellular adhesion molecule-1 expression and to reduce inflammatory cell migration in patients with rhinitis. Well-controlled studies in SAR and VMR demonstrated that Azelastine nasal spray improves nasal symptoms of rhinitis, including congestion and postnasal drip, and has a rapid onset of action that appears likely due to topical activity. Azelastine nasal spray has demonstrated greater efficacy when used in combination with fluticasone propionate nasal spray when compared to either agent alone, and this combination may provide benefit for patients with moderate-to-severe rhinitis. Bitter taste is the most common side effect associated with Azelastine nasal spray and this problem can be mitigated by the dosing technique recommended by the manufacturer in the product labeling. The incidence of somnolence also may be reduced with the recommended administration technique. Conclusions: Azelastine is an effective, rapid-acting, and well-tolerated second-generation antihistamine that improves nasal symptoms associated with SAR and VMR. Clinical studies demonstrated that Azelastine nasal spray can improve symptoms of SAR in patients who remained symptomatic after treatment with oral antihistamines and that Azelastine nasal spray in combination with fluticasone nasal spray provided significantly (p < 0.05) greater relief than either agent alone in patients with SAR.
Intranasal Azelastine. A review of its efficacy in the management of allergic rhinitis
Drugs 1998 Jul;56(1):91-114.PMID:9664202DOI:10.2165/00003495-199856010-00011.
Azelastine, a phthalazinone compound, is a second generation histamine H1 receptor antagonist which has shown clinical efficacy in relieving the symptoms of allergic rhinitis when administered as either an oral or intranasal formulation. It is thought to improve both the early and late phase symptoms of rhinitis through a combination of antihistaminic, antiallergic and anti-inflammatory mechanisms. Symptom improvements are evident as early as 30 minutes, after intranasal administration of Azelastine [2 puffs per nostril (0.56mg)] and are apparent for up to 12 hours in patients with seasonal allergic rhinitis (SAR). The effect on nasal blockage is variable: in some studies objective and/or subjective assessment showed a reduction in blockage, whereas in other studies there was no improvement. Intranasal Azelastine 1 puff per nostril twice daily is generally as effective as standard doses of other antihistamine agents including intranasal levocabastine and oral cetirizine, ebastine, loratadine and terfenadine at reducing the overall symptoms of rhinitis. The relative efficacies of Azelastine and intranasal corticosteroids (beclomethasone and budesonide) remain unclear. However, overall, the corticosteroids tended to improve rhinitis symptoms to a greater extent than the antihistamine. Azelastine was well tolerated in clinical trials and postmarketing surveys. The most frequently reported adverse events were bitter taste, application site irritation and rhinitis. The incidence of sedation did not differ significantly between Azelastine and placebo recipients and preliminary report showed cardiovascular parameters were not significantly altered in patients with perennial allergic rhinitis (PAR). Conclusion: Twice-daily intranasal Azelastine offers an effective and well tolerated alternative to other antihistamine agents currently recommended for the symptomatic relief of mild to severe SAR and PAR in adults and children (aged > or = 12 years in the US; aged > or = 6 years in some European countries including the UK). The rapid onset, confined topical activity and reduced sedation demonstrated by the intranasal formulation of Azelastine may offer an advantage over other antihistamine agents, although this has yet to be confirmed.
Azelastine nasal spray: a review of pharmacology and clinical efficacy in allergic and nonallergic rhinitis
Allergy Asthma Proc 2003 Mar-Apr;24(2):95-105.PMID:12776442doi
Azelastine hydrochloride is a pharmacologically distinct H1-receptor antagonist with a broad spectrum of antiallergic and anti-inflammatory activity. Azelastine has established antiallergic and anti-inflammatory effects that are unrelated to H1-receptor antagonism, including inhibitory effects on the synthesis of leukotrienes, kinins, and cytokines; the generation of superoxide free radicals; and the expression of the intercellular adhesion molecule 1. Azelastine is available in the United States as a nasal spray formulation (Astelin) and is approved for treatment of seasonal allergic rhinitis and nonallergic vasomotor rhinitis. In U.S. clinical trials, Azelastine nasal spray was effective in treating all of the symptoms of the allergic rhinitis symptom complex including ocular symptoms, and in double-blind clinical trials in nonallergic vasomotor rhinitis, Azelastine nasal spray was effective in treating the total vasomotor rhinitis symptom complex including individual symptoms of nasal congestion and postnasal drip. This article reviews the pharmacologic profile and clinical efficacy and safety of Azelastine nasal spray.