Pharmacological characterization of the relaxant effect of RCD405 in isolated human small airways

<bold>Background:</bold> RCD405 is a new investigational agent with an alternative mechanism of action under development for the treatment of asthma and COPD. <bold>Aim:</bold> To pharmacologically characterize the relaxant effect of RCD405 in human small airways. <bold>Methods:</bold> Isolated human small airways (1 mm diameter) were sub-maximally pre-contracted by carbachol (CCh) and histamine (His) at EC70. Concentration-response curves to RCD405 were constructed on the sub-maximal contractile tone induced by His and CCh. Krebs-Henseleit buffer solution was used as negative control. Experiments were conducted on n=5 different small airways. Data on efficacy (Emax) and potency (pEC50) of RCD405 were reported as mean±SE. Statistical significance was set for P<0.05. <bold>Results:</bold> RCD405 was effective in completely relaxing small airways pre-contracted by His (Emax 89.86±5.96%), an effect that was significantly (P<0.01) greater than that induced in CCh pre-contracted small airways (Emax 54.35±6.93). No significant difference (P>0.05) resulted for the potency of RCD405 between His pre-contracted and CCh pre-contracted small airways (pEC50: 4.71±0.10 and 4.78±0.21, respectively). <bold>Conclusions:</bold> RCD405 relaxes human small airways in a concentration-response manner, demonstrating a greater effect on the histaminergic tone compared to the cholinergic tone. The bronchorelaxant effect at the level of small airways provides translatable indications for future clinical trials especially in severe forms of asthma and COPD, as the effect on small airways in vitro is related with improvement in air-trapping 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.