Tracheal relaxant and cardio stimulant actions of xanthines can be differentiated from diuretic and central nervous system stimulant effects role of adenosine antagonism?
Persson, C.G.A.; Erjefalt, I.; Edholm L E.; Karlsson J A.; Lamm C J.
Life Sciences 31(24): 2673-2682
Theophylline (1,3-dimethylxanthine) and enprofylline (3-propyl-xanthine) were examined for effects in the rat. Enprofylline was 3.8 times as potent as theophylline as a tracheal relaxant in vitro, and 1.3 times as potent as theophylline to increase the rate of isolated perfused hearts. An oral dose (5 mg/kg) of enprofylline to rats was almost completely recovered in the urine as unchanged drug, showing that this xanthine is well absorbed and negligibly metabolized. Theophylline (10 and 30 mg/kg (p.o. [orally]) significantly and dose-dependently increased locomotor activity in rats, whereas the same doses of enprofylline were without effect on behavior. Theophylline (5-20 mg/kg p.o.) produced significant and dose-dependent natriuretic and volume diuretic effect with little augmentation of K excretion. Enprofylline up to 10 mg/kg was without diuretic effects. At the large dose of 20 mg/kg enprofylline decreased Na excretion and produced some volume diuresis. Lack of diuretic and CNS-stimulant behavioral effects by enprofylline may be due to its low ability to antagonize adenosine receptor stimulation. Pharmacodynamic differences between enprofylline and the potent adenosine antagonist theophylline may indicate a fucntional importance of endogenous adenosine.