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  • Title: Effects of nonsedating histamine H1-antagonists on EEG activity and behavior in the cat.
    Author: Marzanatti M, Monopoli A, Trampus M, Ongini E.
    Journal: Pharmacol Biochem Behav; 1989 Apr; 32(4):861-6. PubMed ID: 2572005.
    Abstract:
    The central effects of the newly-developed antihistamines (H1-receptor antagonists) loratadine, astemizole, mequitazine and terfenadine were evaluated by studying brain electrical activity (EEG), sleep-waking patterns and behavior in the cat. The different stages of the sleep-waking cycle, i.e., wakefulness (W), spindle sleep (SS), slow wave sleep (SWS) and REM sleep (REM) were evaluated. The power spectrum analysis of the EEG was obtained by a computerized technique. For comparison, the sedating agent diphenhydramine was examined. Given at 3 mg/kg orally, a dose slightly above that effective therapeutically, diphenhydramine markedly affected behavior and all sleep stages. In particular, it depressed REM and increased SS (drowsiness). The EEG showed occasional spikes typical of subconvulsive states. Loratadine did not modify either sleep patterns or behavior over the 3-30 mg/kg dose range orally, which is far above that used clinically. The EEG, evaluated either visually or by spectral power analysis, was unaffected. Astemizole at 10 and 30 mg/kg PO reduced REM, markedly altered behavior at 30 mg/kg, but did not modify EEG activity. Mequitazine, at low doses (1-10 mg/kg PO), enhanced SS and decreased SWS and REM. Like diphenhydramine, mequitazine induced EEG changes typical of subconvulsive states and affected EEG power over the frequency range of 0.1-15.0 Hz. Terfenadine did not change sleep patterns and slightly affected behavior only at the high dose of 30 mg/kg orally; EEG activity was not influenced. These data show that: a) diphenhydramine and mequitazine appear to produce CNS effects by altering basic processes within the brain; b) astemizole and terfenadine seem to cross the blood-brain barrier at high doses only; c) loratadine has the lowest liability to produce central side effects. Of the sleep features examined, REM appeared to be the most sensitive stage to blockade of central H1-receptor pathways.
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