Clinical Investigations

Reproterol - A Monomolecular Combination of Orciprenaline and Theophylline: Novel Aspects of Its Mode of Action in Asthma
Uwe R. Juergens, Meinolf Stöber, Hans Vetter

Department of Pulmonary Diseases, Medical Policlinic, University Hospital, Bonn, Germany

Address of Corresponding Author

Respiration 1999;66:220-224 (DOI: 10.1159/000029381)

  Key Words

• Reproterol
• Orciprenaline
• Theophylline
• cAMP
• Leukotriene B₄

  Abstract

Background and Objective: Reproterol is a monomolecular combination of orciprenaline and theophylline used as -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 -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 × 10⁴ cells/30 min)- and on LPS (10 µg/ml)-stimulated LTB₄ production (10⁵ 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. Conclusion: 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.

  Author Contacts

Dr. U.R. Juergens
Abteilung Pneumologie, Medizinische Universitäts-Poliklinik
Wilhelmstrasse 35-37, D-53111 Bonn (Germany)
Tel. +49 228 287 2227, Fax +49 228 287 2266/2229
E-Mail uwejuergens@t-online.de

  Article Information

Received: Received: July 13, 1998
Accepted after revision: November 26, 1998
Number of Print Pages : 5
Number of Figures : 3, Number of Tables : 0, Number of References : 27