Disease relevance of Viarespan

• Fenspiride: an anti-inflammatory drug with potential benefits in the treatment of endotoxemia [1].
• 2. In the rat, actions on the pulmonary circulation were investigated in the isolated perfused lung, but fenspiride proved to be a poor pulmonary vasodilator, showing only a small reversal of the raised pulmonary artery pressure induced by hypoxia [2].
• Comparison of fenspiride with beclomethasone as adjunctive anti-inflammatory treatment in patients with chronic obstructive pulmonary disease [3].
• CONCLUSION: Anti-inflammatory therapy with fenspiride in addition to bronchodilators significantly improved clinical signs and symptoms, external respiratory function tests and physical activity tests in patients with stage 1 COPD [3].
• Efficacy of Pneumorel 80 mg (fenspiride) in the treatment of chronic sinusitis. Double-blind placebo-controlled study [4].

High impact information on Viarespan

• Here, in rat alveolar macrophages, high fenspiride concentrations (1 mM) were required to inhibit the calcium signals evoked by the calcium agonist Bay K8644 or by ionomycin [5].
• Finally, protein kinase C (PKC) activity of macrophage homogenate was not significantly modified by 10 or 100 microM fenspiride (at 100 microM: 2.57 +/- 1.60 vs. 2.80 +/- 1.71 pmol/10(6) cells/min) [5].
• Moreover, fenspiride (1 mM) was a poor inhibitor of the cell membrane depolarization induced by gramicidine D [5].
• By contrast, fenspiride blocked Na+-H+ antiport activation by (i) fMLP with an IC50 = 3.1 +/- 1.9 nM and (ii) PMA (phorbol 12-myristate 13-acetate) with an IC50 = 9.2 +/- 3.1 nM [5].
• In conclusion, fenspiride inhibits fMLP- and PMA-induced pH signals in rat alveolar macrophages, probably by acting distally on the PKC transduction signal [5].

Chemical compound and disease context of Viarespan

• OBJECTIVE: This study aimed to compare the clinical efficacy of two anti-inflammatory medications (fenspiride and inhaled beclomethasone [beclomethasone dipropionate]) in patients with stable chronic obstructive pulmonary disease (COPD) over 6 months [3].

Biological context of Viarespan

• Whether a pathway common to both cough and bronchoconstriction is the site of action of fenspiride remains to be established [6].
• The absolute bioavailability of fenspiride has been studied in twelve healthy volunteers [7].
• Single dose pharmacokinetics of fenspiride hydrochloride: phase I clinical trial [7].
• Fenspiride therapy significantly reduced the indices of sputum parameters (8-fold decrease), incidence of dry rales (6-fold decrease), dyspnoea (4-fold decrease) and cough (2.5-fold decrease) [3].
• Detection of fenspiride and identification of in vivo metabolites in horse body fluids by capillary gas chromatography-mass spectrometry: administration, biotransformation and urinary excretion after a single oral dose [8].

Anatomical context of Viarespan

• Fenspiride and membrane transduction signals in rat alveolar macrophages [5].
• Blockade by fenspiride of endotoxin-induced neutrophil migration in the rat [9].
• The release of tumour necrosis factor by stimulated macrophages was inhibited by fenspiride in a dose-dependent manner [9].
• In conclusion, the result of this study suggests that fenspiride, in moderate concentrations, reduces the release of neuropeptides, including tachykinins, from sensory nerve endings at a prejunctional level [10].
• We conclude that, in ferret trachea in vitro, fenspiride inhibits neurally-mediated mucus secretion, with antimuscarinic action the most plausible mechanism of action, but not necessarily the only mechanism [11].

Associations of Viarespan with other chemical compounds

• Administered orally at 60 mg/kg, fenspiride reduced the lipopolysaccharide-induced early rise of tumor necrosis factor concentrations in serum (4.2 +/- 0.9 vs. 2.3 +/- 0.5 ng/ml, P < 0.05) and in the bronchoalveolar lavage fluid (55.7 +/- 20 vs. 19.7 +/- 7.5 ng/ml, P < 0.05) [1].
• DESIGN, METHODS AND PATIENTS: This was a randomised comparison of 58 patients with COPD, divided into five treatment groups: fenspiride (stages 1 and 2), beclomethasone (stage 2), and two control groups (stages 1 and 2) [3].

Gene context of Viarespan

• Fenspiride (10(-7)-10(-5) M) inhibited the histamine H1 receptor-induced Ca2+ increase [12].
• RESULTS: Statistically significant reductions in all evaluated COPD signs and symptoms were achieved with fenspiride in stage 1 COPD [3].

Analytical, diagnostic and therapeutic context of Viarespan

• The determination of fenspiride in human plasma and urine by liquid chromatography with electrochemical or ultraviolet detection [13].
• Topically applied fenspiride was found to inhibit the development of sclerotic lesions, whereas intraperitoneal injections were ineffective [14].
• In patients with stage 2 COPD, reductions were less marked, but remained significantly superior in the fenspiride group in comparison with the beclomethasone group and the control groups [3].

References