Disease relevance of azelastine

• Anti-allergic drugs including azelastine prevent immediate-type hypersensitivity by inhibiting mast cell degranulation, as well as blocking histamine H1 receptors [1].
• Azelastine was superior to placebo in improving all individual rhinitis symptoms [2].
• Corticosteroid-sparing effect of azelastine in the management of bronchial asthma [3].
• Apart from a "bitter, metallic" taste in the mouth reported by 41.2% of the patients while they were receiving azelastine, no other unwanted effects were encountered [4].
• CONCLUSIONS: It thus appears that azelastine is superior to chlorpheniramine in suppressing skin responses to histamine and morphine sulfate and in suppressing pruritus in patients with mastocytosis [5].

Psychiatry related information on azelastine

• The late-phase reactions to allergens were less well defined and showed larger individual differences in the degree of inhibition caused by azelastine, they were inhibited by 49% (range 32-67) [6].
• In rats, a high dose of 100 mg/kg azelastine produced a slight suppression of the paradoxical sleep [7].

High impact information on azelastine

• In ionomycin-stimulated cells, however, azelastine inhibited TNF-alpha release to a greater extent than mRNA expression/protein synthesis and Ca2+ influx, suggesting that azelastine inhibits the release process more potently than transcription or production of TNF-alpha by interfering with a signal other than Ca2+ [1].
• Azelastine added 1 h after ionomycin stimulation also immediately blocked subsequent release of TNF-alpha, which had been produced in the cells, without affecting Ca2+ influx [1].
• Suppression of TNF-alpha secretion by azelastine in a rat mast (RBL-2H3) cell line: evidence for differential regulation of TNF-alpha release, transcription, and degranulation [1].
• With these tools, anti-inflammatory activity related to the modulation of epithelial cell adhesion molecules has been demonstrated in vivo for several H(1)-receptor antagonists (azelastine, cetirizine, loratadine, levocabastine, oxatomide, and terfenadine) [8].
• Azelastine nasal spray is a topical antihistamine treatment for the symptoms of seasonal allergic rhinitis [9].

Chemical compound and disease context of azelastine

• METHODS: Fifteen subjects with mastocytosis participated in a double-blind, randomized, three-period, crossover trial, which compared an azelastine regimen of 4 mg or 8 mg every 12 hours with a chlorpheniramine regimen of 12 mg every 12 hours [5].
• 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 [10].
• By contrast, none of the antihistamines tested (azelastine, ketotifen, terfenadine, and cetirizine) suppressed the eosinophil infiltration or dermatitis manifestations [11].
• Evaluation of the onset and duration of effect of azelastine eye drops (0.05%) versus placebo in patients with allergic conjunctivitis using an allergen challenge model [12].
• To identify the chemical mediators involved in the pathogenesis of allergic rhinitis, we studied the effects of the thromboxane (TX) A2 receptor antagonist seratrodast, the peptide leukotriene receptor antagonist pranlukast and the antihistamine azelastine using a guinea pig model of allergic rhinitis [13].

Biological context of azelastine

• In contrast, azelastine had a very low affinity for both beta-receptors and muscarinic receptors with IC50 values greater than 2 logs greater than those determined for beta-agonists and muscarinic antagonists, respectively [14].
• Drugs such as terfenadine and azelastine inhibit early bronchoconstriction and to some extent the late-phase asthmatic response as well [15].
• The geometric means of the dose of histamine (in cumulative breath units [cbu]) necessary to increase specific airway resistance by 100% as compared with baseline (PD100SRaw) were 8.7 and 8.5 cbu before placebo and azelastine, respectively [16].
• After a histamine inhalation test, we randomly administered either placebo or a single oral dose of 8.8 mg azelastine in a double-blind crossover fashion [16].
• In parallel with actions on twitch contractions, azelastine suppressed the amplitude of excitatory junction potentials of dog trachea without changing the resting membrane potential and input resistance of smooth muscle cells [17].

Anatomical context of azelastine

• Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: an antiallergic activity [18].
• Effects of azelastine on vagal neuroeffector transmission in canine and human airway smooth muscle [17].
• The effect of azelastine on neutrophil and eosinophil generation of superoxide [19].
• To examine the mechanism potentially contributing to therapeutic efficacy of azelastine in allergic rhinitis and asthma, we studied the effect of azelastine on stimulated histamine release from basophils prepared as a mixed leukocyte suspension from human blood [20].
• Thus, azelastine, in concentrations achieved therapeutically, inhibited granulocyte generation of O2-. This anti-inflammatory effect may also be beneficial in the treatment of asthma [19].

Associations of azelastine with other chemical compounds

• Duration of the effect of a single dose of azelastine on histamine-induced bronchoconstriction [16].
• In general, the relative order of potency at calculated IC50 level was as follows: azelastine greater than ketotifen greater than theophylline greater than DSCG [21].
• Multicenter, double-blind, multiple-dose, parallel-groups efficacy and safety trial of azelastine, chlorpheniramine, and placebo in the treatment of spring allergic rhinitis [22].
• We performed competitive radioligand binding assays and determined the affinity of azelastine for [3H]pyrilamine (histamine H1), [125I]pindolol (beta), and [3H]quinuclidinyl benzilate (muscarinic) binding sites [14].
• Neither azelastine nor BDP protected against the increase in bronchial responsiveness to methacholine occurring during the pollen season [23].

Gene context of azelastine

• Among the human CYPs tested, the inhibitory effects of azelastine and its two metabolites were the most potent on human CYP2D6 [24].
• The inhibition of CYP2C9, CYP2C19, and CYP3A4 activity by azelastine and its two metabolites might be clinically insignificant [24].
• Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs [25].
• CYP1A2, CYP2A6, and CYP2E1 activities were not significantly inhibited by azelastine and the two metabolites [24].
• Desmethylazelastine, but not azelastine and 6-hydroxyazelastine, uncompetitively inhibited CYP2B6 activity (Ki = 32.6 +/- 4.8 microM) [24].

Analytical, diagnostic and therapeutic context of azelastine

• In a 10-week, multicenter, double-blind, placebo-controlled, crossover study, the efficacy and safety of azelastine, 1 mg and 2 mg twice daily, were evaluated in 192 patients with symptoms of perennial allergic rhinitis [26].
• This article reviews and discusses the antihistaminic and anti-inflammatory properties of azelastine and the results of pharmacokinetic studies and controlled clinical trials [9].
• BDP, but not azelastine, treatment significantly reduced the percent of eosinophils recovered in nasal lavage (p < 0.05) [23].
• In this randomized, double-blind, placebo-controlled, multicenter study, 150 patients, aged 12 to 60 years, with moderate to severe asthma, received a single oral dose of 2, 4, 8, 12, or 16 mg of azelastine or placebo [27].
• Azelastine was well tolerated in clinical trials and postmarketing surveys [28].

References