Effects of methylated xanthines on the neuronally isolated cerebral cortex

Abstract

Although caffeine has long been considered to be a cerebral cortical stimulant, relatively little is known of its sites and mechanism of action in the cerebral cortex. Therefore, the effects of the methylated xanthines, caffeine, theophylline, and theobromine have been studied on the evoked electrical afterdischarge of the neuronally isolated cerebral cortex preparation of dogs. Electrical stimulation of the neuronally isolated island of suprasylvian gyrus with an intact pial circulation in postanesthetized and immobilized dog preparations elicited a characteristic reproducible spikelike discharge limited within the island. The duration of such afterdischarge was measured before and after the administration of various drugs. Among the methylated xanthines, caffeine in doses as low as 0.25 mg/kg was the most potent in prolonging cortical afterdischarge. Theophylline and theobromine appeared much less potent. The dose-effect relationship with different doses of the methylated xanthines was determined. It was found that large doses of theophylline and theobromine clearly reduced the duration of cortical afterdischarge. Repeated administration of caffeine appeared to cause no further or even less prolongation of afterdischarge than that produced by the first dose suggesting that tachyphylaxis occurred.