@article {CalzettaP3337, author = {Luigino Calzetta and Mario Cazzola and Clive Page and Paola Rogliani and Francesco Facciolo and Maria Gabriella Matera}, title = {Interaction between RPL554 and glycopyrronium bromide in small human airways}, volume = {44}, number = {Suppl 58}, elocation-id = {P3337}, year = {2014}, publisher = {European Respiratory Society}, abstract = {Background:The relaxant synergistic interaction between RPL554 and anticholinergic agents has been recently proved on human isolated segmental bronchi (Calzetta, L. et al. J Pharmacol Exp Ther. 2013;346:414-23).Aim:To investigate the interaction between RPL554 and glycopyrronium in human isolated bronchioles.Methods:Precision cut lung slices (PCLSs) from 6 patients were incubated in Krebs-Henseleit solution (37{\textdegree}C) aerated with O2/CO2 (95:5\%). The concentration response to RPL554 and glycopyrronium, administered alone and in combination at isoeffective concentrations, was assessed at sub-maximal contraction (70\% maximum, EC70) induced by carbachol (CCh). The relaxation of small bronchi (\<1mm diameter) was expressed as \% of maximal response (lumen area enhancement) induced by papaverine (Emax) and potency as negative logarithm of IC50 (pD2). Drug mixture effects were analyzed by Bliss Independence theory. Values (n=3) are mean{\textpm}SEM.Results:Glycopyrronium induced a more potent concentration-dependent relaxation of bronchioles compared with RPL554 (pD2: glycopyrronium 9.2{\textpm}0.4, RPL554 6.0{\textpm}0.1, P\<0.001) and both abolished the CCh-induced contraction. Glycopyrronium and RPL554 at low-to-middle concentrations (glycopyrronium 0.05nM{\textendash}0.14 nM, RPL554 0.32{\textmu}M{\textendash}0.54{\textmu}M) had a synergistic relaxant effect on small airway enhancing relaxation by +21.1{\textpm}4.0\%, compared with the expected response (P\<0.05). Low concentrations (EC30) of glycopyrronium plus RPL554 induced significant (P\<0.05) lumen area enhancement of 69.1{\textpm}2.4\%, compared with the expected response (51.0{\textpm}5.4\%).Conclusions:RPL554 and glycopyrronium had a synergistic interaction on the lumen area enhancement of bronchioles, mainly at low-to-middle concentrations.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/44/Suppl_58/P3337}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }