地西泮与咪达唑仑对orexin A作用的影响

Influence of diazepam and midazolam on the effect of orexin A

目的观察地西泮和咪达唑仑对大脑皮质切片中orexin A作用的影响。方法应用高效液相色谱-电化学检测器法研究了地西泮和咪达唑仑对大脑皮质中orexin A引起的去甲肾上腺素释放的影响。结果地西泮和咪达唑仑剂量-依赖性降低orexin A引起的去甲肾上腺素的释放。咪达唑仑的半数抑制浓度(IC50)为0.87μmol/L,地西泮为68.5μmol/L,咪达唑仑显著低于地西泮(P<0.01)。这种抑制作用并不被中枢性苯二氮卓受体拮抗剂氟马西尼所拮抗(P>0.05)。结论地西泮和咪达唑仑能够抑制orexin能神经元,而这种抑制作用可能不是通过苯二氮卓类受体起作用。

Objective To study the influence of diazepam and midazolam on orexin A in rat cerebrocortical slices.Methods High performance liquid chromatography（HPLC） was used to observe the influence of diazepam and midazolam on orexin A-evoked norephinephrine release in rat cerebrocortical slices.Results Diazepam and midazolam concentration-dependently inhibited orexin A-evoked norepinephrine release.The IC50 of midazolam for orexin A-evoked norepinephrine release（0.87 μmol/L,P〈0.01）was significantly lower than that of diazepam（68.5 μmol/L）.The inhibitory effects on orexin A-evoked norepinephrine release was not changed by flumazenil,a central benzodiazepine antagonist（P〉0.05）.Conclusion The present study suggests that diazepam and midazolam may significantly inhibit orexinergic neurons.However,this inhibition could not be mediated via benzodiazepine receptors.