Evaluation of the effect of different routes of administrating flumazenil against hypnosis
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摘要: 目的 研究氟马西尼不同给药途径对受地西泮和唑吡坦催眠小鼠的催醒作用，评价氟马西尼口服制剂的可行性。 方法 首先，昆明种小鼠分别腹腔注射生理盐水和戊巴比妥钠（S+W）、地西泮和戊巴比妥钠（D+W）、唑吡坦和戊巴比妥钠（Z+W），观察（D+W）组和（Z+W）组能否延长戊巴比妥钠睡眠时间，验证地西泮和唑吡坦的催眠效果；然后提前腹腔注射给药氟马西尼，以小鼠睡眠时间为评价指标，评价其催醒作用；最后考察提前灌胃给药氟马西尼，观察其睡眠时间，评价氟马西尼灌胃给药的催醒作用。 结果 与对照组（S+W）相比，地西泮组（D+W）和唑吡坦组（Z+W）能显著延长戊巴比妥钠诱导的小鼠睡眠时间（P<0.001，P<0.05）；提前腹腔注射或灌胃给药氟马西尼，与地西泮组（D+W）和唑吡坦组（Z+W）相比，小鼠的睡眠时间显著缩短（P<0.001，P<0.05）。 结论 氟马西尼无论是腹腔注射还是灌胃给药，均能拮抗地西泮和唑吡坦的催眠作用，表明氟马西尼制成的口服制剂，同样能显著发挥药效，为研制氟马西尼口服制剂的可行性提供了依据。Abstract: Objective To study the effect of flumazenil on hypnotic mice induced by diazepam and zolpidem, and to evaluate the possibility of flumazenil oral administration. Methods First, Kunming mice were injected intraperitoneally with normal saline and sodium pentobarbital (S + W), diazepam and pentobarbital sodium (D + W), zolpidem and pentobarbital sodium (Z + W). The hypnotic effect of diazepam and zolpidem on prolonging the sleep time of pentobarbital sodium would be verified by (D + W) group and (Z + W) group. Then the mice were injected intraperitoneally with flumazenil. The sleep time was used as the evaluation index to evaluate the effect of flumazenil against hypnosis. Finally, the oral administration of flumazenil was observed against hypnosis, which was evaluated by using sleep time as an index. Results Compared with the control group (S+W), the diazepam group (D+W) and the zolpidem group (Z+W) significantly prolonged the sleep time induced by pentobarbital sodium (P<0.001,P<0.05);After Intraperitoneal injection of flumazenil,compared with the diazepam group (D+W) and the zolpidem group (Z+W),the sleep time of the diazepam group[F(ip)+D+W] and the zolpidem group[F(ip)+Z+W] were significantly shorter (P<0.001, P<0.05);After oral administration of flumazenil, the sleep time of the diazepam group[F(ig)+D+W] and the zolpidem group[F(ig)+Z+W] were also significantly shorter (P<0.001,P<0.05). Conclusion Flumazenil, whether intraperitoneal injection or intragastric administration, could antagonize the hypnotic effect of diazepam and zolpidem. It was proved that oral administration of flumazenil had the same effect compared with intraperitoneal injection of flumazenil, which provided the possibility of preparation of oral administration of flumazenil.
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Key words:
- flumazenil /
- diazepam /
- zolpidem /
- hypnosis /
- against hypnosis
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[1] 徐利君, 徐仙娥, 林利芬. 镇静催眠药物的研究进展[J]. 海峡药学, 2014, 26(11):17-21. [2] 李洪涛, 吴秀云, 赵芹,等. 氟马西尼对丙泊酚复合舒芬太尼全麻患者血浆中食欲素A的影响[J]. 中国临床研究, 2017, 30(5):592-595. [3] Trotti LM, Saini P, Koola C, et al. Flumazenil for the treatment of refractory hypersomnolence:clinical experience with 153 patients[J]. J Clin Sleep Med, 2016, 12(10):1389-1394. [4] 王芝燕. 地西泮-布洛芬栓制备及质量标准研究[J]. 临床合理用药杂志, 2016, 9(35):89-90. [5] 叶晨静, 龚艳春. 失眠症的临床治疗及效果评定[J]. 中国实用医药, 2017, 12(6):124-125. [6] 刘正. 建立镇静催眠药临床前药效学评价方法和研究西红花有效成分的催眠作用及机制[D]. 上海:复旦大学, 2010. [7] 中华人民共和国卫生部. 新药(西药)临床前研究指导原则汇编[M]. 中华人民共和国卫生部药政局, 1993. [8] Forouzanfar F, Hosseini A, Amiri M S, et al. Potentiating effects of Perovskia abrotanoides Karel. on pentobarbital-induced sleep[J]. Avicenna J Phytomed, 2017, 7(3):214-222. [9] Koga N, Yamaguchi T, Lee KK, et al. Kososan,a standardized traditional Japanese herbal medicine, reverses sleep disturbance in socially isolated mice via GABAA-benzodiazepine receptor complex activation[J]. Phytomedicine, 2014, 21(5):697-703. [10] Roncari G, Ziegler WH, Guentert TW. Pharmacokinetics of the new benzodiazepine antagonist Ro 15-1788 in man following intravenous and oral administration[J]. Br J Clin Pharmacol, 1986, 22(4):421-428. [11] Klotz U, Kanto J. Pharmacokinetics and clinical use of flumazenil (Ro 15-1788)[J]. ClinPharmacokinet, 1988, 14(1):1-12. [12] Kasteleijn-Nolst Trenite DG, Groenwold RH, Schmidt B,et al. Single dose efficacy evaluation of two partial benzodiazepine receptor agonists in photosensitive epilepsy patients:A placebo-controlled pilot study[J]. Epilepsy Res, 2016, 122:30-36. -
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