Mucociliary clearance in COPD can be increased by both a D2/[formula omitted]2 and a standard [formula omitted]2 agonists

Abstract

In addition to breathlessness and cough, excessive mucus production is one of the main symptoms of chronic obstructive pulmonary disease (COPD). Excess mucus coupled with deteriorating mucociliary clearance is associated with a decline in lung function and an increased risk of death from pulmonary infection. The effect of Viozan (Sibenadet HCl, AR-C68397AA), a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, on mucociliary clearance was investigated together with that of a beta2-adrenoceptor agonist, salbutamol. Using a double blind, parallel group study design, 15 patients with COPD, all habitual smokers, were randomised to receive nebulised sidenadet (3mg tid; n = 7) or salbutamol (5mg tid; n = 8) for 10 days. Lung mucociliary clearance rates were measured, by a standard radioaerosol technique, before and after the treatment period, as were 24-h sputum volumes. Both sibenadet and salbutamol therapies resulted in significant (P<0.02) enhancement of lung mucociliary clearance. The 24-h sputum volume was significantly reduced following sibenadet therapy (P<0.03) whereas salbutamol therapy had no effect. Our results, in addition to illustrating the effects of a standard beta2 agonist on mucociliary clearance, strongly suggest the potential dual benefit of dual-agonist compounds in lessening sputum production whilst simultaneously enhancing mucociliary clearance. For reasons unconnected with the present study, development work on this specific formulation is no Longer proceeding.