Related Experiment Video

Updated: Mar 28, 2026

Subcutaneous Administration of Muscarinic Antagonists and Triple-Immunostaining of the Levator Auris Longus Muscle in Mice

Subcutaneous Administration of Muscarinic Antagonists and Triple-Immunostaining of the Levator Auris Longus Muscle in Mice

Published on: September 8, 2011

Interaction between corticosteroids and muscarinic antagonists in human airways

Mario Cazzola¹, Luigino Calzetta², Paola Rogliani³

¹University of Rome Tor Vergata, Department of Systems Medicine, Chair of Respiratory Medicine, Rome, Italy; University of Rome Tor Vergata, Department of Systems Medicine, Respiratory Pharmacology Research Unit, Rome, Italy; University Hospital Tor Vergata, Division of Respiratory Medicine, Rome, Italy.

Pulmonary Pharmacology & Therapeutics

|December 15, 2015

Abstract

Background:

To date there is emerging clinical evidence to add long-acting anti-muscarinic agents (LAMAs) with inhaled corticosteroid (ICSs) in asthma, but the pharmacological rationale that supports the use of such a combination has not yet been explained. The aim of this study was to pharmacologically investigate the interaction between the ICS beclomethasone and the LAMA glycopyrronium on the human airway smooth muscle (ASM) tone.

Methods:

We investigated the rapid non-genomic bronchorelaxant effect of beclomethasone and glycopyrronium, administered alone and in combination, in human isolated bronchi and bronchioles. Experiments were carried out also in passively sensitized airways and the pharmacological analysis of drug interaction was performed by Bliss Independence method.

Results:

The acute administration of beclomethasone and glycopyrronium induced a significant relaxation of passively sensitized ASM pre-contracted with histamine, by causing submaximal/maximal inhibition of the contractile tone in both medium bronchi and bronchioles. Beclomethasone was characterized by a rapid non-genomic and epithelium independent bronchorelaxant effect. In passively sensitized airways, this effect seemed to be dependent by the activation of a Gsα--cyclic adenosine monophosphate (cAMP)--protein kinase A cascade. While no synergistic interaction was detected in non-sensitized bronchi, the beclomethasone/glycopyrronium combination synergistically enhanced the relaxation of passively sensitized medium and small bronchi. The synergistic interaction between beclomethasone and glycopyrronium was associated with an increase of cAMP concentrations.

Conclusions:

Our study provides for the first time the pharmacological rationale for combining low doses of an ICS plus a LAMA.

Keywords:

Airway smooth muscle Asthma Drug interaction ICS LAMA

More Related Videos

In vitro Measurements of Tracheal Constriction Using Mice

In vitro Measurements of Tracheal Constriction Using Mice

Published on: June 25, 2012

Assessment of Respiratory Function in Conscious Mice by Double-chamber Plethysmography

Assessment of Respiratory Function in Conscious Mice by Double-chamber Plethysmography

Published on: July 10, 2018

Related Concept Videos

Antiasthma Drugs: Muscarinic Receptor Antagonists

Antiasthma Drugs: Muscarinic Receptor Antagonists

Muscarinic receptor antagonists, also known as antimuscarinic agents, are a class of bronchodilators used to treat asthma, although they are more commonly used to treat COPD. They work by inhibiting the action of acetylcholine (ACh), a neurotransmitter, on muscarinic receptors found in the airways.
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...

Cholinergic Antagonists: Pharmacological Actions

Cholinergic Antagonists: Pharmacological Actions

Antimuscarinic drugs block muscarinic receptors in multiple systems, including the gut, eye, smooth muscles, respiratory tract, cardiovascular, and central nervous systems. They produce similar effects with varying selectivity depending on the specific agent and tissue. Here are the key pharmacological actions of antimuscarinics:
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...

Cholinergic Antagonists: Pharmacokinetics

Cholinergic Antagonists: Pharmacokinetics

Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations, while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and...

Cholinergic Antagonists: Therapeutic Uses

Cholinergic Antagonists: Therapeutic Uses

Antimuscarinic drugs have various therapeutic applications by inhibiting parasympathetic stimulation in different systems. Here are the key therapeutic uses of antimuscarinics:
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal...

Direct-Acting Cholinergic Agonists: Pharmacological Actions

Direct-Acting Cholinergic Agonists: Pharmacological Actions

Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...

Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids

Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids

Inhaled corticosteroids (ICS) are anti-inflammatory drugs used primarily in treating persistent asthma and providing long-term maintenance. They target the bronchial mucosa, the lining of the airways, to control inflammation, a critical factor in asthma progression and exacerbation.
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...

Articles linked to this work by shared authors, journal, and citation graph.

Bronchorelaxant and anti-inflammatory profile of ensifentrine alone and combined with inhaled medications in lipopolysaccharide-challenged human airways from chronic obstructive pulmonary disease donors.

The Journal of pharmacology and experimental therapeutics·2026

A Delphi consensus report of the Italian society of thoracic surgery on influencing factors, use of a bleeding scale, and management of bleeding in thoracic surgery.

Frontiers in surgery·2026

Validation of the 9th Edition of the TNM Classification in Patients with NSCLC and Lymph Node Involvement: A Retrospective, Multicentric, Observational Study.

Cancers·2026

Evaluation of high flow nasal cannulae during endobronchial ultrasound bronchoscopy (EBUS) in high anaesthetic risk patients: a monocentric prospective study.

BMC anesthesiology·2025

Lung involvement in psoriatic arthritis patients: cross-sectional study on prevalence, clinical characteristics, and risk factors of a neglected comorbidity.

Clinical and experimental rheumatology·2025

Real-World Effectiveness of Triple Extrafine Fixed-Dose Combination with Beclomethasone/Formoterol/Glycopyrronium on Symptoms and Lung Function in COPD: A Systematic Review and Meta-Analysis.

International journal of chronic obstructive pulmonary disease·2025

See all related articles