(ii)For the treatment of chronic obstructive pulmonary disease (COPD), the Italian company Chiesi Farmaceutici in collaboration with Charles River Laboratories very recently combined antagonism at the M3 mAChR with inhibition of phosphodiesterase 4 (PDE4) in a so-called MAPI drug candidate (compound 10f; Fig. 2) that showed a balanced bronchodilator / anti-inflammatory profile in rats [35]. The gene discussed is PDE4A; the disease is chronic obstructive pulmonary disease.