The behavioral and electroencephalographic effects of alprazolam and its metabolites were investigated in mice, rats and rabbits, and compared with the data on diazepam, lorazepam and nitrazepam. Locomotor activity of mice in an open-field situation was increased with smaller doses of alprazolam and nitrazepam but not with diazepam and lorazepam. Alprazolam increased the hyperactivity induced by methamphetamine in mice. The anticonflict effects of alprazolam in rats were more potent than those of diazepam and lorazepam. In suppressing hyperemotionality and muricide of olfactory bulbectomized rats, alprazolam was more potent than diazepam and fairly equal to that of lorazepam. Muricide of raphe-lesioned rats was markedly inhibited by alprazolam. Mescaline-induced head-twitches in mice were more markedly increased with alprazolam than with nitrazepam and diazepam. Alprazolam, diazepam and lorazepam prevented both maximal electroshock and pentetrazol convulsions in mice. Alprazolam was more potent than diazepam and lorazepam in potentiating thiopental, ether and ethanol anesthesia in mice. In the impaired rotarod performance, alprazolam was more potent than diazepam and lorazepam in mice, but was much less potent than lorazepam in rats. In conscious rabbits with chronically implanted electrodes, alprazolam induced a drowsy EEG pattern and depressed the EEG arousal response not only to auditory stimulation but also to mesencephalic reticular stimulation. The EEG effect of alprazolam was approx. twice that of diazepam. The pharmacological activity of a-hydroxyalprazolam was approx. one third that of alprazolam. However, 5-chloro-2-(3-hydromethy1-5-methyl-4H-1, 2,4-triazolo-4-y1) benzophenone showed no pharmacological activity. These results indicate that alprazolam possesses pharmacologic properties characteristic to benzodiazepines and that the activity is more potent than diazepam. In addition, alprazolam seems to have a specific effect on the central seroto nergic mechanisms.
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