Pharmacological characterization of the relaxant effect of RCD405 in isolated human medium bronchi

<bold>Background:</bold> RCD405 is a new drug candidate under development for the treatment of chronic obstructive pulmonary disorders that targets both inflammation and bronchoconstriction. <bold>Aim:</bold> To pharmacologically characterize the relaxant effect of RCD405 in human medium bronchi. <bold>Methods:</bold> Isolated human sub-segmental bronchi (4 mm diameter) were sub-maximally pre-contracted by carbachol (CCh) and histamine (His) at EC70. Bronchial contractility was also elicited by electrical field stimulation (EFS). Concentration-response curves to RCD405 were constructed on CCh and His pre-contracted bronchi and on EFS. Krebs-Henseleit buffer solution was used as negative control (C-). Experiments were conducted on n=5 different rings. Data were reported as mean±SE and statistical significance set for P<0.05. <bold>Results:</bold> RCD405 completely relaxed bronchial rings pre-contracted by CCh (Emax 92.12±3.90%) and His (Emax 96.25±1.45%). The potency of RCD405 was significantly (P<0.001) greater in His pre-contracted than in CCh pre-contracted bronchi (pEC50: 4.93±0.08 vs. 4.34±0.06, respectively). RCD405 significantly reduced the bronchial tone induced by EFS 25Hz (Emax 63.27±10.24%, P<0.05 vs. C-) and EFS 50Hz (Emax 79.32±8.94, P<0.001 vs. C-). <bold>Conclusions:</bold> RCD405 relaxes human sub-segmental bronchi in a concentration-response manner. The efficacy and potency profile of RCD405 against both the cholinergic and histaminergic tone provides translatable results for future clinical trials in asthma and COPD, as the effect on sub-segmental bronchi in vitro is related with improvement in FEV1 in clinical setting (1). This study was supported by Arcede Pharma AB (Sweden). 1. Calzetta et al., Br J Pharmacol. 2024 Mar;181:610-639.