Ueki S, Sukamoto T, Watanabe S, Yamamoto T, Kataoka Y, Shibata S, Suwandi D, Shibata K, Takano M, Sato Y
Nihon Yakurigaku Zasshi. 1982 Jul;80(1):15-30.
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 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.
研究了KB - 509及其代谢产物的行为效应，并在小鼠和大鼠中将其与地西泮的行为效应进行了比较。通过Animex试验测量，相对大剂量的KB - 509和地西泮可降低小鼠的自发活动。KB - 509对大鼠的抗冲突效应与地西泮大致相当。地西泮以50mg/kg口服剂量可降低未受惩罚期的杠杆按压反应，而即使是100mg/kg口服的大剂量KB - 509也不会对其产生影响。KB - 509在口服剂量高达1000mg/kg时，能极大剂量抑制大鼠在穿梭箱中的条件性回避反应。KB - 509的这种效应比地西泮弱得多。在抑制小鼠足部电击诱导的攻击行为方面，KB - 509比地西泮更有效。KB - 509和地西泮可预防小鼠最大电休克、戊四氮和士的宁诱导的惊厥。在增强巴比妥麻醉、损害转棒试验表现以及通过小鼠牵引试验测量的肌肉松弛活性方面，KB - 509比地西泮更有效。去烷基 - KB - 509的药理活性比KB - 509更强，而去烷基 - 3 - OH - KB - 509的药理活性与KB - 509大致相当。这些结果表明，KB - 509具有与地西泮相似的药理特性，其效力略强于地西泮，作用持续时间比地西泮长得多。
