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 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 alpha-hydroxyalprazolam was approx. one third that of alprazolam. However, 5-chloro-2-(3-hydromethyl-5-methyl-4H-1, 2,4-triazolo-4-yl) 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 serotonergic mechanisms.

Aggression↗

PubMed1981

Mode of the excitatory and inhibitory actions of ciguatoxin in the guinea-pig vas deferens.

Ciguatoxin (CTX), one of the most potent known toxic substances among marine toxins, causes a contraction in the isolated guinea-pig vas deferens at the concentration of above 3 x 10(-7) g/ml. The CTX-induced contraction of the vas deferens was inhibited or abolished by a treatment with phentolamine or guanethidine, but not affected in the presence of atropine or mecamylamine. Furthermore, this contraction was blocked by a treatment with tetrodotoxin, procaine or cold storage and incubation in a low Na+ medium. On the other hand, CTX markedly potentiated the contraction of vas deferens which was induced by norepinephrine (NE), acetylcholine or high-K, whereas it inhibited the contractile response to transmural stimulation. CTX caused a marked release of NE from the adrenergic nerves, which was blocked after treatment with tetrodotoxin or incubation in a Ca-free medium. On the basis of these results, it is suggested that the CTX-induced contraction is the result of an indirect action mediated through the NE release from the adrenergic nerve terminals and that the effect of NE released from the presynaptic sites is potentiated by CTX at the postsynaptic sites. The inhibitory effect of CTX on the contractile response to transmural stimulation may be due to decreasing the transmitter release caused by stimulation.

Animals↗

PubMed1981