Reproterol--A monomolecular combination of orciprenaline and theophylline: novel aspects of its mode of action in asthma.
OBJECTIVE
Reproterol is a monomolecular combination of orciprenaline and theophylline used as beta-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 beta-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 x 10(4) cells/30 min)- and on LPS (10 microg/ml)-stimulated LTB4 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 LTB4 was significantly inhibited by reproterol (-48 +/- 14%) and less by theophylline (-28 +/- 10%), but was stimulated by orciprenaline (+20 +/- 8%) at 10(-5) M.


CONCLUSIONS
We conclude that reproterol exerts a strong stimulatory effect on monocyte cAMP production and a suppressive effect on LTB4 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.
Juergens
U R
UR
Department of Pulmonary Diseases, Medical Policlinic, University Hospital, Bonn, Germany. uwejuergens@t-online.de
Stöber
M
M
Vetter
H
H
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D001993:Bronchodilator Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D004338:Drug Combinations; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis; D009921:Metaproterenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012016:Reference Values; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001993:Bronchodilator Agents; D004338:Drug Combinations; C014792:reproterol; D007975:Leukotriene B4; D009921:Metaproterenol; D013806:Theophylline; D000242:Cyclic AMP