氟马西尼不同给药途径的催醒作用评价

Evaluation of the effect of different routes of administrating flumazenil against hypnosis

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。

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.