The mechanism responsible for the drowsiness caused by first generation H-1 antagonists on the EEG pattern

The present study was performed to clarify the mechanism responsible for th e drowsiness caused by first generation H-1 antagonists according to electr oencephalogram activity. All H-1 antagonists used on the present study caus ed the EEG-recorded drowsiness pattern, i.e., increases in EEG power spectr a of the delta and theta bands at the frontal cortex in rats. The potency o f cyproheptadine was greater than those of diphenydramine and promethazine, while that of pyrilamine was less than those of the other drugs examined. The increase in EEG power spectra in the delta band induced by H-1 antagoni sts was antagonized by pretreatment with both histidine and physostigime. T he effect of pyrilamine was more potently antagonized by histidine and less potently antagonized by physostigmine as compared to diphenylhydramine, pr omethazine and cyproheptadine. The increases in EEG power spectra induced b y H-1 antagonists were neither antagonized nor potentiated by 5-hydroxytryp tophan. These results clearly indicate that the increases in EEG power spec tra in the delta and theta bands at the frontal cortex in rats induced by f irst generation H-1 antagonists are responsible for both histaminergic and cholingeric mechanisms. (C) 2000 Prous Science. All rights reserved.