Different approaches in the treatment of obstructive pulmonary diseases

Kabir, Eva Rahman; Morshed, Nabila

doi:10.1016/j.ejphar.2015.07.030

Cited by 6 publications

(3 citation statements)

References 79 publications

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“…Nonetheless, the present findings and others from the literature bolster the hypothesis that RLX deserves to be further investigated as a new drug for the treatment of CS-induced COPD. Indeed, the current therapies for COPD, primarily based on corticosteroids and bronchodilators, have improved disease management but cannot prevent disease progression (Barnes, 2010;Kabir and Morshed, 2015). Rather, at the doses and administration times effective to control COPD, glucocorticoids can cause unwanted local and systemic side effects (Kelly and Nelson, 2003).…”

Section: Discussionmentioning

confidence: 99%

Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin (Serelaxin)

Pini

Boccalini

Lucarini

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD), which is characterized by airway remodeling, lung inflammation and fibrosis, emphysema, and respiratory failure. The current therapies can improve COPD management but cannot arrest its progression and reduce mortality. Hence, there is a major interest in identifying molecules susceptible of development into new drugs to prevent or reduce CS-induced lung injury. Serelaxin (RLX), or recombinant human relaxin-2, is a promising candidate because of its anti-inflammatory and antifibrotic properties highlighted in lung disease models. Here, we used a guinea pig model of CSinduced lung inflammation, and remodeling reproducing some of the hallmarks of COPD. Animals exposed chronically to CS (8 weeks) were treated with vehicle or RLX, delivered by osmotic pumps (1 or 10 mg/day) or aerosol (10 mg/ml/day) during CS treatment. Controls were nonsmoking animals. RLX maintained airway compliance to a control-like pattern, likely because of its capability to counteract lung inflammation and bronchial remodeling. In fact, treatment of CS-exposed animals with RLX reduced the inflammatory recruitment of leukocytes, accompanied by a significant reduction of the release of proinflammatory cytokines (tumor necrosis factor a and interleukin-1b). Moreover, RLX was able to counteract the adverse bronchial remodeling and emphysema induced by CS exposure by reducing goblet cell hyperplasia, smooth muscle thickening, and fibrosis. Of note, RLX delivered by aerosol has shown a comparable efficacy to systemic administration in reducing CS-induced lung dysfunction and damage. In conclusion, RLX emerges as a new molecule to counteract CS-induced inflammatory lung diseases.

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Section: Discussionmentioning

confidence: 99%

Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin (Serelaxin)

Pini

Boccalini

Lucarini

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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“…Additionally, other factors including exposure to indoor air pollutions from biomass fuels, particularly in developing countries, occupational dusts, chemicals, and genetics, may also contribute toward disease morbidity and mortality [ 63 , 64 ]. Currently, the pharmacological management of COPD mainly relies on bronchodilator therapy, mainly β 2 -agonists and anticholinergics, by activating different signaling pathways [ 65 , 66 , 67 , 68 ]. β 2 -Agonists induce airway smooth muscle (ASM) cell relaxation through enhanced intracellular cAMP production, whereas anticholinergics or antimuscarinic drugs antagonize muscarinic receptors (M1, M2 and M3) to a certain extent, thus inhibiting ASM contraction, due to the reduction of intracellular Ca 2+ .…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

Epac Function and cAMP Scaffolds in the Heart and Lung

Laudette

Zuo

Lezoualc’h

et al. 2018

JCDD

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Evidence collected over the last ten years indicates that Epac and cAMP scaffold proteins play a critical role in integrating and transducing multiple signaling pathways at the basis of cardiac and lung physiopathology. Some of the deleterious effects of Epac, such as cardiomyocyte hypertrophy and arrhythmia, initially described in vitro, have been confirmed in genetically modified mice for Epac1 and Epac2. Similar recent findings have been collected in the lung. The following sections will describe how Epac and cAMP signalosomes in different subcellular compartments may contribute to cardiac and lung diseases.

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“…Bronchodilators are the mainstay of pharmacological treatment of COPD ( Anzueto and Kaplan, 2020 ). Two classes of bronchodilators can be distinguished: β 2 -adrenoreceptor agonists and muscarinic antagonists ( Kabir and Morshed, 2015 ; van Haarst et al, 2019 ; Calzetta et al, 2021 ), with long-acting bronchodilators considered to provide more convenient and effective symptom relief than short-acting bronchodilators ( Quinn et al, 2018 ). Long-acting muscarinic antagonists (LAMAs) are recommended as the first-line maintenance bronchodilator therapy in patients with stable COPD without significant symptoms but who have a high risk of exacerbations and those without a history of exacerbation but with significant symptoms ( Rhee et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, metabolite profiling, safety, and tolerability of inhalation aerosol of 101BHG-D01, a novel, long-acting and selective muscarinic receptor antagonist, in healthy Chinese subjects

Gao

Chen³

et al. 2022

Front. Pharmacol.

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101BHG-D01 is a novel, long-acting, selective muscarinic receptor antagonist for the treatment of chronic obstructive pulmonary disease (COPD). A single-site, randomized, double-blind, placebo-controlled and dose-escalation study of 101BHG-D01 inhalation aerosol was conducted to evaluate its pharmacokinetics, metabolite profiling, safety and tolerability following the single inhaled doses ranged from 20 to 900 μg in healthy Chinese subjects. After inhalation, 101BHG-D01 was absorbed rapidly into plasma with the time to maximum concentration about 5 min, and eliminated slowly with the terminal phase half-life about 30 h. The cumulative excretion rates of 101BHG-D01 in feces and urine were about 30% and 2%, respectively, which showed the study drug was mainly excreted in feces. The maximum drug concentration and area under the plasma concentration-time curve increased with dose escalation in the range of 20–600 μg, but their values increased out of proportion to the whole studied doses. The main metabolic pathways were loss of phenyl group and hydroxylation. No metabolite that presented at greater than 10 percent of total drug-related exposure was observed. 101BHG-D01 was safe and well tolerated after administration. The study results indicate that 101BHG-D01 is a good candidate for the treatment of COPD and enable further clinical development in subsequent studies in patients.Clinical Trial Registration:http://www.chinadrugtrials.org.cn; Identifier: CTR20192058.

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Different approaches in the treatment of obstructive pulmonary diseases

Cited by 6 publications

References 79 publications

Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin (Serelaxin)

Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin (Serelaxin)

Epac Function and cAMP Scaffolds in the Heart and Lung

Pharmacokinetics, metabolite profiling, safety, and tolerability of inhalation aerosol of 101BHG-D01, a novel, long-acting and selective muscarinic receptor antagonist, in healthy Chinese subjects

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