The mechanism responsible for the drowsiness caused by first generation H1 antagonists on the EEG pattern.

The present study was performed to clarify the mechanism responsible for the drowsiness caused by first generation H1 antagonists according to electroencephalogram activity. All H1 antagonists used in the present study caused the EEG-recorded drowsiness pattern, i.e., increases in EEG power spectra of the delta and theta bands at the frontal cortex in rats. The potency of cyproheptadine was greater than those of diphenhydramine 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 H1 antagonists was antagonized by pretreatment with both histidine and physostigmine. The effect of pyrilamine was more potently antagonized by histidine and less potently antagonized by physostigmine as compared to diphenhydramine, promethazine and cyproheptadine. The increases in EEG power spectra induced by H1 antagonists were neither antagonized nor potentiated by 5-hydroxytryptophan. These results clearly indicate that the increases in EEG power spectra in the delta and theta bands at the frontal cortex in rats induced by first generation H1 antagonists are responsible for both histaminergic and cholinergic mechanisms.