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 orci prenaline and theophylline used as beta-adrenergic agonist to induce bronch odilation 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 whethe r the theophylline component of the reproterol molecule might enhance the s timulatory effect of the beta-adrenoceptor on cAMP production resulting in suppression of inflammatory mediator production. Methods: The effects of re proterol, orciprenaline and theophylline (10(-9)-10(-5) M) on spontaneous c AMP (5 x 10(4) cells/30 min)and on LPS (10 mu g/ml)-stimulated LTB4 product ion (10(5) cells/4 h) were determined in normal monocytes in vitro. Results : Production of cAMP (n = 9) was significantly augmented in a dose-dependen t manner by orciprenaline (30 +/- 8%) and theophylline (28 +/- 10%), but mo stly by reproterol (127 +/- 8%) at 10(-5) M. Despite incubation with propra nolol, significant stimulation of cAMP production was notable following rep roterol therapy. Production of LTB4 was significantly inhibited by reproter ol (-48 +/- 14%) and less by theophylline (-28 +/- 10%), but was stimulated by orciprenaline (+20 +/- 8%) at 10-5 M. Conclusion: We conclude that repr oterol exerts a strong stimulatory effect on monocyte cAMP production and a suppressive effect on LTB4 production possibly due to a synergistic mode o f action on adenylate cyclase activity and inhibition of phosphodiesterases . More clinical studies in bronchial asthma will be needed to determine whe ther these results may translate into clinically relevant effects.