The sedative potential of mizolastine, a new, potent and selective antagonist of histamine H1-receptors, has been evaluated in the rodent with EEG techniques. In chronically implanted rabbits, sedation was observed in ECoG recordings after intravenous injection of terfenadine (1–10 mg/kg) and loratadine (0.3–3 mg/kg) but not after intravenous injection of astemizole or mizolastine (1–10 mg/kg). In freely moving implanted rats, mizolastine and cetirizine (10 mg/kg i.p.) did not modify the sleep-wakefulness pattern recorded during the dark period nor did mizolastine alter the sleep architecture recorded in rats during the light period. In contrast, during the dark-period recording, astemizole, loratadine and terfenadine (10 mg/kg i.p.) increased the total duration of slow-wave sleep; this sleep-facilitating effect had a late onset of action, beginning 3 h after drug injection. In conclusion, the results obtained with astemizole, cetirizine, loratadine and terfenadine demonstrate their low sedative potential in the rat, and suggest that the absence or low incidence of sedation seen in humans with these drugs may be due to their limited ability to cross the blood brain-barrier, especially at recommended therapeutic doses. Mizolastine appears to be devoid of sedative effects in our experimental models irrespective of the route of administration used. These results predict a lack of sedative action in humans with mizolastine at therapeutic doses.

Keywords:
Mizolastine, H1-receptor antagonists, Sedation, EEG, Sleep-wakefulness cycle, Rabbit, Rat
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© 1995 S. Karger AG, Basel
1995
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