A novel bronchodilator xanthine apparently without adenosine receptor antagonism and tremorogenic effect

Enprofylline is a potent bronchodilating xanthine derivative that has been shown to have little or no ability to antagonize adenosine in a variety of cell types. In eight patients with chronic obstructive lung disease, a single dose of enprofylline (3.5 mg/kg) was given orally. A double blind, randomized, crossover comparison was made with oral theophylline (9.5 mg/kg) which is a potent and general adenosine receptor antagonist. Forced expiratory volume (FEV1), vital capacity, tremor of hands, heart rate, and blood pressure were followed for 6 h. Plasma concentrations of both drugs were monitored. At doses producing significant bronchodilation, theophylline caused a significant increase in tremor of hands whereas enprofylline did not. There were no significant changes in heart rate or blood pressure after either drug. It is suggested that the lack of tremorogenic effect of enprofylline is related to its lack of CNS-stimulating behavioural effects and, hence, may reflect its low tendency to antagonize neuro-depressant actions of adenosine. The adenosine-blocking mechanism may not be important for the bronchodilating effects of xanthines.