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[单独使用以及与抗抑郁药联合使用时,利苏瑞ide对抑郁动物模型的影响]

[Effects in animal models of depression of lisuride alone and upon coadministration with antidepressants].

作者信息

Nakamura K, Ikoma Y, Kimura K, Nakada Y, Kobayashi S, Yamaguchi M, Nakagawa H

机构信息

Research Department, Nihon Schering K.K., Osaka, Japan.

出版信息

Nihon Yakurigaku Zasshi. 1989 Jul;94(1):81-9. doi: 10.1254/fpj.94.81.

Abstract

Effects of lisuride, a central dopamine and serotonin agonist of the ergot type, in animal models of depression were investigated in comparison with those of desipramine, mianserin and rolipram. Lisuride, like desipramine and mianserin, inhibited reserpine-induced hypothermia in mice (0.5-5.0 mg/kg, i.p.) and suppressed muricide in olfactory bulbectomized rats (ED50 = 0.16 mg/kg, i.p.) in a dose-dependent manner. The anti-muricidal effect was slightly enhanced by the repeated administration of 0.25 mg/kg lisuride. Lisuride (0.05-0.25 mg/kg, i.p.), like desipramine, dose-dependently reduced the duration of immobility in rats forced to swim, and this effect was antagonized by haloperidol. The reduction of immobility time was enhanced by the repeated administration of lisuride; at the same time, the ambulation in rats increased. Furthermore, the immobility-reducing effects of desipramine and rolipram were markedly enhanced by the co-administration of a low dose of lisuride (0.025 mg/kg, i.p.), which by itself had no effect on the immobility time. These results indicate that lisuride may be useful for the treatment of depression and indicate that a low dose of lisuride may enhance the clinical effectiveness of antidepressants such as desipramine.

摘要

将麦角型中枢多巴胺和血清素激动剂利苏立得在抑郁症动物模型中的作用与地昔帕明、米安色林和咯利普兰进行了比较研究。利苏立得与地昔帕明和米安色林一样,能剂量依赖性地抑制小鼠(腹腔注射0.5 - 5.0 mg/kg)由利血平引起的体温过低,并抑制嗅球切除大鼠的杀鼠行为(腹腔注射的半数有效剂量为0.16 mg/kg)。重复给予0.25 mg/kg利苏立得可使抗杀鼠作用略有增强。利苏立得(腹腔注射0.05 - 0.25 mg/kg)与地昔帕明一样,能剂量依赖性地缩短强迫游泳大鼠的不动时间,且该作用可被氟哌啶醇拮抗。重复给予利苏立得可增强不动时间的缩短;同时,大鼠的活动增加。此外,联合给予低剂量利苏立得(腹腔注射0.025 mg/kg)可显著增强地昔帕明和咯利普兰的减少不动作用,而利苏立得本身对不动时间无影响。这些结果表明利苏立得可能对抑郁症治疗有用,并表明低剂量利苏立得可能增强地昔帕明等抗抑郁药的临床疗效。

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