Reproterol – A Monomolecular Combination of Orciprenaline and Theophylline: Novel Aspects of Its Mode of Action in Asthma

Background and Objective: Reproterol is a monomolecular combination of orciprenaline and theophylline used as β-adrenergic agonist to induce bronchodilation in bronchial asthma. Since the mechanism of action of reproterol has not been investigated so far, its potential anti-inflammatory activity in asthma remains still unknown. Therefore, we have studied in vitro whether the theophylline component of the reproterol molecule might enhance the stimulatory effect of the β-adrenoceptor on cAMP production resulting in suppression of inflammatory mediator production. Methods: The effects of reproterol, orciprenaline and theophylline (10 –9 –10 –5 M) on spontaneous cAMP (5 × 10 4 cells/30 min)- and on LPS (10 μg/ml)-stimulated LTB 4 production (10 5 cells/4 h) were determined in normal monocytes in vitro. Results: Production of cAMP (n = 9) was significantly augmented in a dose-dependent manner by orciprenaline (30 ± 8%) and theophylline (28 ± 10%), but mostly by reproterol (127 ± 8%) at 10 –5 M. Despite incubation with propranolol, significant stimulation of cAMP production was notable following reproterol therapy. Production of LTB 4 was significantly inhibited by reproterol (–48 ± 14%) and less by theophylline (–28 ± 10%), but was stimulated by orciprenaline (+20 ± 8%) at 10 –5 M. Conclusion: We conclude that reproterol exerts a strong stimulatory effect on monocyte cAMP production and a suppressive effect on LTB 4 production possibly due to a synergistic mode of action on adenylate cyclase activity and inhibition of phosphodiesterases. More clinical studies in bronchial asthma will be needed to determine whether these results may translate into clinically relevant effects.