Characterisation of the novel quinoline RCD405: Relaxant effects on cholinergic and histaminergic tone in human bronchi and small airways

Abstract Background and Purpose Increased contractility of human airway smooth muscle (hASM) is a hallmark of asthma and chronic obstructive pulmonary disease (COPD). Developing new classes of bronchodilators has proved to be challenging because of efficacy and safety concerns. Quinolines hold potential therapeutic applications for the treatment of respiratory disorders. Experimental Approach Relaxant effects of the novel quinoline RCD405 were investigated on contractile responses of hASM to carbachol, histamine and electrical field stimulation (EFS). The role of the non‐adrenergic non‐cholinergic (NANC) system was assessed using the inducible NO synthase inhibitor aminoguanidine and the TRPV1 agonist capsaicin. Key Results In medium bronchi, RCD405 elicited a maximum relaxant effect ( E max ) of 92 ± 4% with a half‐maximal effective concentration (EC 50 ) of 45.71 μM for carbachol, and an E max of 96 ± 1% with a EC 50 of 12 μM for histamine. In small airways, RCD405 demonstrated significant relaxant responses, with an E max of 54 ± 7% (EC 50 17 μM) for carbachol and 90 ± 6% (EC 50 20 μM) for histamine. RCD405 reduced contractility in response to EFS, with E max values of 63 ± 10% at 25 Hz and 79 ± 9% at 50 Hz in medium bronchi. The NANC system did not affect the bronchorelaxation induced by RCD405. Conclusions and Implications RCD405 showed significant potential as a novel bronchodilator drug for the treatment of asthma and COPD through its ability to induce relaxation of hASM. These findings suggest that further investigation of RCD405 is warranted as a possible novel treatment of chronic respiratory disorders.