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Brain Res Bull. 1989 Feb;22(2):271-5.

Excitatory effect of histamine on the arousal system and its inhibition by H1 blockers.

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Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.


To clarify whether the sedative effect of H1 blockers is exerted in relation to H1 receptors in the brain, EEG activity recorded from the cortex and thalamus of rats was studied by power spectral analysis. EEG processing was performed by the FFT method and displayed as compressed spectral arrays. When a train of low frequency electrical stimulation was applied to the midbrain reticular formation of conscious rats, there was an increase in spectral power recorded at the cortex and thalamus, especially in the low frequency bands (0-6 Hz). The intraventricular administration of histamine suppressed the increase in power; this inhibition was antagonized by simultaneous administration of pyrilamine or diphenhydramine, though not in in combination with cimetidine or ranitidine. As in the case of histamine, the administration of 2-methylhistamine decreased power in the slow wave region, while administration of 4-methylhistamine did not. It was assumed that the arousal effect of histamine is exerted via H1 and not related to H2 receptors. Adverse effects of H1 blockers, such as drowsiness, may be caused by their inhibition of histamine's arousal effect.

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