Disease relevance of formoterol

• Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease [1].
• The magnitude and duration of protection against exercise-induced asthma (EIA) afforded by salbutamol and the new, long-acting beta 2-agonist, formoterol, were compared in a double-blind, placebo-controlled crossover study [2].
• Neither formoterol nor salmeterol elicit significant cardiovascular effects in healthy individuals and patients with reversible airway obstruction [3].
• The most commonly encountered adverse effects in clinical trials with combination budesonide/formoterol therapy have been respiratory infection, pharyngitis and coughing [4].
• However, adverse cardiac events might occur in patients with COPD with pre-existing cardiac arrhythmias and hypoxaemia if they use long-acting 12 agonists, although the recommended single dose of salmeterol 50 microg or formoterol 12 microg ensures a relatively higher safety margin than formoterol 24 microg [3].

Psychiatry related information on formoterol

• Maintenance plus as-needed budesonide/formoterol prolonged the time to first severe exacerbation versus salmeterol/fluticasone (25% risk reduction) [5].
• The long acting beta-adrenergic agonists formoterol and salmeterol give protection against exercise-induced airway obstruction for up to 12 h, which implies that treatment given in the morning will offer protection from the effects of physical activity throughout the day [6].
• Formoterol, which is the only beta2-agonist to possess both fast- and long-acting properties, may help to improve patient compliance by allowing a single inhaler to be used for both maintenance and as-needed therapy [7].

High impact information on formoterol

• METHODS: We assessed the effect of formoterol and budesonide on the activation and function of transcription factors by immunohistochemistry, western blotting, DNA mobility shift assay, and a luciferase reporter gene assay [8].
• The four beta 2-adrenoceptor agonists, clenbuterol, bambuterol, formoterol and salmeterol, are all long-acting bronchodilators, that have distinct mechanisms for their extended durations of action [9].
• For all formoterol regimens, the bronchodilator response 1 hour after inhalation was maintained over the 2-week treatment period [10].
• Opposing actions of (R,R)-isomers and (S,S)-isomers of formoterol on T-cell function [11].
• Short-acting beta(2)-agonists (eg, albuterol) and long-acting beta(2)-agonists (eg, salmeterol, formoterol) inhibit cell activation, inflammatory mediator release, and cell recruitment and survival mechanisms in vitro, with evidence of cellular specificity in response [12].

Chemical compound and disease context of formoterol

• The kinetics of inhaled racemic formoterol and its effects on the size of the early cutaneous reaction to intradermal injection of an allergen, eosinopenia and hypokalemia were assessed by pharmacokinetic-pharmacodynamic modeling [13].
• The findings indicate that formoterol has considerably more powerful anabolic effects on skeletal muscle than older generation beta(2)-agonists (like clenbuterol and albuterol), and has considerable therapeutic potential for muscular dystrophies and other neuromuscular disorders where muscle wasting is indicated [14].
• Both treatments partially correct muscle atrophy without modifying IGF-1 and atrogin-1 mRNA levels, whereas MuRF1 hyperexpression is reduced by the combination of pentoxifylline with formoterol [15].
• The effects of formoterol (BD 40A) on the rat and guinea-pig hypersensitivity reactions and on mouse IgE antibody formation was investigated [16].
• Prolonged bronchodilating effect of formoterol versus procaterol in bronchial asthma [17].

Biological context of formoterol

• Inhaled formoterol in the prevention of exercise-induced bronchoconstriction in asthmatic children [18].
• METHODS: A total of 24 patients with asthma (forced expiratory volume in 1 second, < or = 70% predicted) inhaled single doses (12 micrograms or 24 micrograms) of formoterol solution and suspension so that we could investigate the immediate tremor, airway, and cardiovascular responses in a randomized, double-blind, crossover trial [19].
• Budesonide or formoterol at 10(-)(8) M inhibited upregulation of CD11b to 26 [15 to 40]% and 38 [23 to 46]%, respectively, and inhibited L-selectin shedding to 14 [-3 to 50]% and 27 [2 to 62]%, respectively, of control values [20].
• CONCLUSIONS: Formoterol and salmeterol cause dose related changes in heart rate, diastolic blood pressure, and plasma glucose and potassium concentrations [21].
• The relative dose potency for formoterol compared with salmeterol at four and eight hours for the different end points excluding systolic blood pressure ranged from 1.6 to 7.0 after adjusting for baseline values [21].

Anatomical context of formoterol

• After formoterol treatment there was a significant decrease in eosinophils and the epithelial expression of activated NF-kappaB, but these changes were not accompanied by reduced immunoreactivity for adhesion molecules or cytokines [22].
• Anti-edema action of formoterol in rat trachea does not depend on capsaicin-sensitive sensory nerves [23].
• In the indirect method, both budesonide and formoterol inhibited lung fibroblast activation, resulting in diminished eosinophil activation after 4 h [20].
• In a double-blind parallel-group study, we evaluated the effect of adding formoterol to a low dose of budesonide, compared with a higher dose of budesonide, on the composition of induced sputum [24].
• Studies performed on airway smooth muscle in vitro have indicated that salmeterol is a partial agonist on the beta2-receptor in comparison to formoterol [25].

Associations of formoterol with other chemical compounds

• The bronchoprotective effect of formoterol Turbohaler 9 microg was compared with salbutamol 200 microg and placebo at 15 min, 4 and 8 h postdose in a randomized, double-blind, placebo-controlled, crossover study [26].
• Salbutamol and formoterol each significantly reduced histamine-induced bronchoconstriction, even in the ozone-exposed animals [27].
• We conclude that formoterol is more effective than ipratropium bromide in the treatment of COPD, as the efficacy of ipratropium on airflow obstruction does not translate into a clinical benefit that patients can perceive [1].
• The results of Ala- and Phe-substituted mutants indicated that the phenyl group of Tyr(308) interacted with the phenyl group in the N-substituent of formoterol (hydrophobic interaction), and the hydroxyl group of Tyr(308) interacted with the protonated amine of procaterol (hydrophilic interaction) [28].
• The therapeutic efficacy of inhaled formoterol has been equal to or greater than that of salbutamol (albuterol), fenoterol and terbutaline in both short and long term clinical trials [29].

Gene context of formoterol

• RESULTS: Formoterol exerted an additive effect on the inhibition of IL-1beta stimulated ICAM-1 and VCAM-1 upregulation and GM-CSF production by budesonide in concentrations of 10(-9) M and above (p<0.05) [30].
• The glucocorticoid budesonide and the long-acting beta2-adrenoceptor agonist formoterol are used in asthma therapy for their anti-inflammatory and bronchodilating effects, respectively [31].
• Serum marker measurements in the formoterol group showed decreased concentrations of eosinophil blood count, ECP, and IL-4, but there was no difference in before and after measurements of sIL-2R, sICAM-1, and IgE [32].
• Budesonide and formoterol inhibit ICAM-1 and VCAM-1 expression of human lung fibroblasts [31].
• The beta adrenergic agonist, formoterol hemifumarate, led to increases in K+ flux into MDA-MB-453 cells, and this increase was inhibited by the GIRK channel inhibitor clozapine [33].

Analytical, diagnostic and therapeutic context of formoterol

• In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide [34].
• Patients were randomly assigned inhaled placebo or inhaled formoterol 24 micrograms bid for 4 weeks each in a crossover study [35].
• Regular formoterol treatment in mild asthma. Effect on bronchial responsiveness during and after treatment [36].
• The evaluation of the mean percentage decrease in FEV1 confirmed the results in favor of formoterol in both the exercise tests [18].
• PC20 values at 36, 60, and 108 h and at 2 wk after formoterol treatment cessation were not significantly different from those after placebo [36].

References