New bronchodilator could be used to control asthma

Researchers have identified a promising drug candidate for the control of lung inflammation and airway constriction. According to the researchers, their new, first-class bronchodilator may help patients with asthma or chronic obstructive pulmonary disease (COPD) control their symptoms.

Despite advances in the management of asthma and chronic obstructive pulmonary disease (COPD), poorly controlled symptoms of both respiratory diseases can lead to severe shortness of breath, hospitalizations, or even death.

“Only about 50 percent of asthmatics, and an even smaller percentage of people with COPD, achieve adequate control of lung inflammation and airway constriction with currently available drugs. So there is clearly something missing in our arsenal of drugs to help all of these patients, ”said Dr. Stephen Liggett, associate dean of research at the University of South Florida (USF) Morsani College of Medicine, States. United, and professor of medicine at USF Health, molecular pharmacology and physiology, and biomedical engineering.

In asthma and COPD, tightening of the smooth muscles surrounding the bronchi narrows the airways and reduces air flow. Dr. Liggett’s lab has discovered several subtypes of bitter taste receptors (TAS2Rs) – G-protein-coupled receptors expressed on muscle cells of the human smooth airways inside the lungs – that can dilate the airways when they are activated. They are now working to identify potential therapies for asthma and other obstructive pulmonary diseases that target TAS2R.

T5-8: a promising bronchodilator

In a preclinical study, published in ACS Pharmacology and translational science, the scientists identified and characterized 18 new compounds that activate the TAS2R5 subtype to promote relaxation of smooth muscle cells in the human airways. First, they assessed the extent to which these novel agonists activated TAS2R5 in airway smooth muscle cells isolated from non-asthmatic human donor lungs, and then validated the effect on airway smooth muscle relaxation using magnetic torsion cytometry, a technique developed by professor Dr. Steven An. of Pharmacology at Rutgers Robert Wood Johnson Medical School and a study collaborator.

Of these agonists, 1,10 phenanthroline-5,6-dione (T5-8) was found to be the most promising: it was 1000 times more potent than some of the other compounds tested and exhibited a significantly higher maximum relaxation response. to that of albuterol (50 percent and 27 percent, respectively). Albuterol is a beta-2 agonist, the only class of direct bronchodilators available to treat wheezing and shortness of breath caused by asthma and COPD. However, this drug or its derivatives – prescribed in rescue inhalers – do not work for all patients and overuse has been linked to an increase in hospitalizations, according to Dr. Liggett. “Having two distinct classes of drugs that work in different ways to open the airways would be an important step in helping patients to optimally control their symptoms.”

He added that while T5-8 worked best, some of the other drug candidates also worked well, “so we now have several potential new drugs to carry out the next steps”, and concluded: “This study has resulted in a drug discovery that successfully meets most of the criteria necessary to advance the compound to its first trial as a potential leading bronchodilator targeting the airway receptor TAS2R5. “