Disease relevance of Mizolastine

• Anaphylaxis to mizolastine [1].
• Mizolastine 10 mg/day is effective in allergic rhinitis and chronic idiopathic urticaria [2].
• Lack of behavioural toxicity of mizolastine: a review of the clinical pharmacology studies [3].
• Furthermore, mizolastine dose-dependently inhibited HERG1 K(+) channels constitutively expressed in SH-SY5Y human neuroblastoma clonal cells [4].
• RESULTS: Mizolastine delayed the cold-induced wheal reaction, reduced wheal response at 3 and 10 minutes, and reduced pruritus intensity [5].

Psychiatry related information on Mizolastine

• Effects of mizolastine, a new antihistamine, on psychomotor performance and memory in elderly subjects [6].
• In contrast, 2 mg clemastine induced significant impairments (decrease in critical flicker fusion, increase in recognition reaction time) in comparison with placebo and mizolastine, although it did not impair memory [6].

High impact information on Mizolastine

• Mizolastine is a new histamine H1 receptor antagonist [2].
• Clinical pharmacokinetics of mizolastine [2].
• The absolute bioavailability of mizolastine 10mg tablets is about 65% [2].
• Concomitant administration of mizolastine and ketoconazole increased mizolastine AUC values with no change in t1/2beta [2].
• Mizolastine appears in vivo to be a relatively weak inhibitor of cytochrome P450 2E1, 2C9, 2D6 and 3A4 [2].

Chemical compound and disease context of Mizolastine

• BACKGROUND: Mizolastine is a nonsedating H1 histamine receptor antagonist with additional antiallergic properties currently marketed in Europe for the treatment of seasonal and perennial allergic rhinitis (PAR) and urticaria [7].
• The combination of mizolastine and ASA can be strongly recommended as a protective measure against UV erythema development with a lower unwanted side effect profile than that of the hitherto treatment modality, i.e. indomethacin [8].
• Double-blind challenge tests with mizolastine, loratadine, fexofenadine, dexchlorpheniramine, ebastine, ketotifen, and placebo were negative, whereas hydroxyzine and its active metabolite, cetirizine, reproduced the urticaria [9].

Biological context of Mizolastine

• Significant increases in theophylline Cmin and AUC were observed after coadministration with mizolastine [2].
• In this paper we present an overview of five clinical pharmacology studies which were carried out with a view to assessing mizolastine effects on psychomotor and skilled performances, and on cognitive functions in young and aged subjects [3].
• Furthermore, with long-term use of mizolastine over 1 year, a reduction in pruritus and the number of urticarial episodes was maintained with no evidence of tachyphylaxis or tolerance [10].
• A population analysis of the kinetics of mizolastine was performed from concentrations on 449 allergic patients, using the nonparametric maximum likelihood method (NPML) [11].
• CONCLUSION: PKC-mediated phosphorylation of Akt can be blocked by mizolastine [12].

Anatomical context of Mizolastine

• Therefore, mizolastine differentially regulates the production of mediators from basophils and mast cells in a cell- and stimulus-specific fashion [13].
• Differential modulation of mediator release from human basophils and mast cells by mizolastine [13].
• 3. Mizolastine blocked HERG1 K(+) channels expressed in XENOPUS: oocytes with an estimated IC(50) of 3.4 microM [4].
• Therefore, primary human skin fibroblasts were incubated with mizolastine or dexamethasone after 100 mJ/cm(2) UVB irradiation [14].
• Regarding T lymphocyte proliferation, the addition of mizolastine did not induce any significant change; furthermore, mizolastine was ineffective at all of the tested concentrations on both HLA-DR expression and CD4+/CD8+ ratio [15].

Associations of Mizolastine with other chemical compounds

• In contrast, mizolastine enhanced up to 80% IgE-mediated histamine release (EC(50): 4.63+/-0.14 microM) from basophils, but not from mast cells and it significantly potentiated IL-4 release from basophils induced by anti-IgE [13].
• METHODS AND RESULTS: Mizolastine (10(-7)-10(-5) M) concentration-dependently inhibited the release of cysteinyl leukotriene C4 from anti-IgE-stimulated basophils (IC(50): 3.85+/-0.28 microM) and mast cells (IC(50): 3.92+/-0.41 microM) [13].
• CONCLUSIONS: Mizolastine efficiently inhibits LTC4 synthesis in human basophils and mast cells presumably by interfering with 5-lipoxygenase [13].
• OBJECTIVE: The aim of this European multicenter, randomized, double-blind study was to compare the efficacy of mizolastine 10 mg (n = 122), cetirizine 10 mg (n = 125), and placebo (n = 128) once daily for 28 days in patients with seasonal allergic rhinoconjunctivitis (SAR), with focus on the onset of action [16].
• It was found that 0.01 mM mizolastine inhibited UVB-induced LTB4 production from skin fibroblasts at 12, 24 and 36 h [14].

Gene context of Mizolastine

• CONCLUSIONS: This study demonstrated that mizolastine is able to selectively downregulate CD54 expression on stimulated stromal but not epithelial cells without impairing the immune system effectors [15].
• Moreover, HaCaT keratinocytes were incubated with mizolastine under various UV treatment modalities in vitro to study its effect on the release of inflammatory cytokines, i.e. interleukin (IL)-1 alpha, IL-6 and tumor necrosis factor alpha (TNF-alpha) [8].
• An inhibitory effect in vitro of 10 nM mizolastine upon UV-induced cytokine release from HaCaT keratinocytes was observed for IL-1 alpha at 24 h after 10 J/cm2 UVA1, for IL-6 at 48 h after 10 J/cm2 UVA1 and 30 mJ/cm2 UVB, and also for TNF-alpha at 4 h after 10 J/cm2 UVA, 10 J/cm2 UVA1 and 30 mJ/cm2 UVB, respectively [8].
• Cells were stimulated with interferon (IFN)-gamma (500 IU/ml) in the presence of various mizolastine concentrations (6 x 10(-8)-6 x 10(-6) M) for 24 h and the expression of CD106, CD54, CD58 and HLA class I was evaluated [15].
• An interaction of desloratadine with P-gp has been suggested in mice, whereas the information on mizolastine is very poor [17].

Analytical, diagnostic and therapeutic context of Mizolastine

• METHODS: Fifteen healthy volunteers participated in this double-blind crossover study and randomly received single doses of 5, 10, 15, and 20 mg of mizolastine and placebo at 1 week intervals [18].
• In addition, mizolastine displays low lipophilicity and consequently low cardiac tissue fixation [19].
• The efficacy of mizolastine, a new non-sedating H1 antagonist, has been evaluated in several placebo-controlled and comparative clinical trials [20].
• CONCLUSION: ECG monitoring of volunteers and patients included in clinical studies conducted with mizolastine showed no significant effect of mizolastine on cardiac repolarization [21].
• The highest dose of mizolastine (6 x 10(-6) M), corresponding to 10-fold the peak plasma level after a single oral administration of 10 mg, was able to act on fibroblasts, significantly downregulating the expression of CD54 (p<0.05) [15].

References