SEIZURE ACTIVITY IN ANIMALS GIVEN ENPROFYLLINE AND THEOPHYLLINE, 2 XANTHINES WITH PARTLY DIFFERENT MECHANISMS OF ACTION

Abstract

Theophylline, a potent adenosine receptor antagonist, and enprofylline (3-propylxanthine), which seems to lack antagonism of neuronal depressant effects of adenosine, where tested for convulsive activity in 3 animal species. In urethane-anesthetized guinea pigs, theophylline produced massive generalized convulsions. Enprofylline was without any seizure activity but produced about the same changes as theophylline in heart rate, blood pressure, respiratory rate (less marked) and blood gas status. The infused LD of enprofylline was about twice as large as that of theophylline. Enprofylline is .apprx. 5 times more potent than theophylline as a bronchodilator. In conscious guinea pigs, mice and cats, enprofylline was devoid of theophylline-like seizure activity. The CNS-stimulant effects of LD of theophylline progressed until death occurred. The major behavioral effects of LD of enprofylline, in contrast, were inhibition of activity and sedation. Evidently, the lack of seizure-activity reflects the inability of enprofylline to antagonize neuronal depressant effects of endogenous adenosine.