Yamamoto T, Shibata S, Teshima K, Inoue Y, Ushio M, Tominaga K, Ohno M, Watanabe S, Ueki S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Nihon Yakurigaku Zasshi. 1991 Jul;98(1):41-52. doi: 10.1254/fpj.98.1_41.
The behavioral and EEG effects of the 5-HT1A partial agonist ipsapirone were investigated to determine its pharmacological characteristics as an anxiolytic drug in rats, mice and rabbits, as compared with those of buspirone and diazepam. 1) The anticonflict effect of ipsapirone was almost equipotent as that of buspirone and less potent than that of diazepam in rats. Ro15-1788 antagonized the anticonflict effect of diazepam, but did not that of ipsapirone. 2) Muricide in midbrain raphe-lesioned and olfactory bulbectomized rats was inhibited by ipsapirone. However, the inhibition of muricide by ipsapirone was attenuated by its repeated administration. 3) The muscle relaxant effects of ipsapirone and buspirone on rotarod performance were less potent than that of diazepam. Ethanol-induced muscle relaxation was markedly potentiated by diazepam, but less potently by ipsapirone and buspirone. 4) The pentetrazol-induced convulsion was dose-dependently antagonized by diazepam, while it was weakly potentiated by ipsapirone and buspirone. 5) The limbic afterdischarges induced by either hippocampal or amygdaloid stimulation in rabbits were markedly inhibited by diazepam. Conversely, ipsapirone and buspirone slightly potentiated afterdischarges. In conclusion, it is suggested that ipsapirone has anxiolytic activities similar to that of buspirone and moderate antimuricidal action. In addition, ipsapirone, like buspirone, is also characterized by its less potent muscle relaxant, alcohol-potentiating and anticonvulsant actions.
研究了5-羟色胺1A受体部分激动剂伊沙匹隆的行为和脑电图效应，以确定其作为抗焦虑药物在大鼠、小鼠和兔子中的药理学特性，并与丁螺环酮和地西泮进行比较。1） 在大鼠中，伊沙匹隆的抗冲突效应与丁螺环酮几乎相当，但比地西泮弱。Ro15-1788拮抗地西泮的抗冲突效应，但不拮抗伊沙匹隆的抗冲突效应。2） 伊沙匹隆可抑制中脑缝际核损伤和嗅球切除大鼠的杀鼠行为。然而，重复给药会减弱伊沙匹隆对杀鼠行为的抑制作用。3） 伊沙匹隆和丁螺环酮对转棒试验的肌肉松弛作用比地西泮弱。乙醇诱导的肌肉松弛在地西泮作用下明显增强，但在伊沙匹隆和丁螺环酮作用下增强作用较弱。4） 戊四氮诱导的惊厥可被地西泮剂量依赖性拮抗，而伊沙匹隆和丁螺环酮则使其轻度增强。5） 地西泮可显著抑制兔海马或杏仁核刺激诱导的边缘叶后放电。相反，伊沙匹隆和丁螺环酮可使后放电略有增强。总之，提示伊沙匹隆具有与丁螺环酮相似的抗焦虑活性和适度的抗杀鼠作用。此外，与丁螺环酮一样，伊沙匹隆的特点还包括其较弱的肌肉松弛、酒精增强和抗惊厥作用。
