The behavioral effects of KB-509 and its metabolites were investigated and compared with those of diazepam in mice and rats. The locomotor activity of mice measured by an Animex test was decreased with relatively large doses of KB-509 and diazepam. The anticonflict effect of KB-509 in rats was approximately as potent as that of diazepam. The lever pressing responses in the unpunished period were reduced by diazepam at a dose of 50 mg/kg p.o., while they were not affected by KB-509 even at a large dose such as 100 mg/kg p.o. KB-509 inhibited conditioned avoidance responses of the rat in a shuttle box at an extremely large dose such as 1000 mg/kg p.o. This effect of KB-509 was much less potent than that of diazepam. KB-509 was more potent than diazepam in inhibiting footshock-induced fighting behavior in mice. KB-509 was more potent than diazepam in suppressing hyperemotionality, but was less potent than diazepam in inhibiting muricide of olfactory bulbectomized rats. KB-509 and diazepam prevented maximal electroshock, pentetrazol, and strychnine induced convulsions in mice. KB-509 was more potent than diazepam in potentiating barbital anesthesia, in impairing rotarod performance, and in muscle relaxant activity measured by a traction test in mice. The pharmacological activity of desalkyl-KB-509 was more potent than that of KB-509 and that of desalkyl-3-OH-KB-509 was approximately as potent as that of KB-509. These results indicate that KB-509 possesses pharmacological properties similar to that of diazepam, and it is slightly greater in potency and is much longer in duration of action than diazepam.
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