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 δ and θ 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 δ 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 δ and θ bands at the frontal cortex in rats induced by first generation H₁ antagonists are responsible for both histaminergic and cholinergic mechanisms. (C) 2000 Prous Science.