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Article Navigation >  Journal of Pharmaceutical Practice and Service  > 2018  >  36(1): 30-33,54

HOU Cheng, LU Guangzhao, ZHANG He, LU Ying, ZHONG Yanqiang, ZOU Hao. Evaluation of the effect of different routes of administrating flumazenil against hypnosis[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(1): 30-33,54. doi: 10.3969/j.issn.1006-0111.2018.01.006
Citation: HOU Cheng, LU Guangzhao, ZHANG He, LU Ying, ZHONG Yanqiang, ZOU Hao. Evaluation of the effect of different routes of administrating flumazenil against hypnosis[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(1): 30-33,54. doi: 10.3969/j.issn.1006-0111.2018.01.006
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Evaluation of the effect of different routes of administrating flumazenil against hypnosis

doi: 10.3969/j.issn.1006-0111.2018.01.006

  • Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

  • Received Date: 2017-09-28
  • Rev Recd Date: 2017-10-23
  • 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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    [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.
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Evaluation of the effect of different routes of administrating flumazenil against hypnosis

doi: 10.3969/j.issn.1006-0111.2018.01.006
  • Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
  • Received Date: 2017-09-28
  • Rev Recd Date: 2017-10-23

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.

HOU Cheng, LU Guangzhao, ZHANG He, LU Ying, ZHONG Yanqiang, ZOU Hao. Evaluation of the effect of different routes of administrating flumazenil against hypnosis[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(1): 30-33,54. doi: 10.3969/j.issn.1006-0111.2018.01.006
Citation: HOU Cheng, LU Guangzhao, ZHANG He, LU Ying, ZHONG Yanqiang, ZOU Hao. Evaluation of the effect of different routes of administrating flumazenil against hypnosis[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(1): 30-33,54. doi: 10.3969/j.issn.1006-0111.2018.01.006
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