[Theophylline--past present and future]

Since its discovery as component of the tea leaf by Albert Kossel in 1888, the history of theophylline (CAS 58-55-9) has been a long and successful one. At the turn of the century, theophylline became less expensive due to chemical synthesis and was primarily used as diuretic in subsequent years. It was Samuel Hirsch who discovered the bronchospasmolytic effect of theophylline in 1992, however, despite this pioneering discovery theophylline continued to be used primarily as diuretic and cardiac remedy. Even when in 1936 the favourable effect of theophylline in the asthmatic state had been highlighted, this finding hardly propagated the use of this drug. Only after the pharmacokinetics and metabolism of theophylline had been elucidated and sustained release preparations had been developed in the 1970s did the substance finally experience a boost. Aside from the known relaxation of the smooth bronchial muscles, studies performed on theophylline revealed an increase in mucociliar clearance and an improvement in diaphragmatic contraction. A dose-effect relationship was described which allowed for the first time to optimise theophylline serum concentrations. In the 1980s it has become generally accepted that the pathogenesis of asthma is based on a chronic inflammatory reaction and that bronchoconstriction is the consequence rather than the cause of this disease. The unique role of theophylline both as reliever of the symptoms and as controller of the underlying asthmatic disease is reflected in the current discussion on a possible inclusion of theophylline in the list of basic therapeutic agents for the treatment of asthma.