Little H J, Bichard A R
Br J Anaesth. 1984 Oct;56(10):1153-60. doi: 10.1093/bja/56.10.1153.
The effects of the benzodiazepine antagonist Ro 15-1788 20 mg kg-1 after "general anaesthetic" doses of several benzodiazepines were studied in mice, in order to determine if the effects of the latter were attributable to an action at benzodiazepine receptors. Male CDI mice were used and the end-points for anaesthesia were loss of the righting reflex and loss of the foot pinch reflex. The effects of midazolam, and to a lesser extent those of chlordiazepoxide and of diazepam on these reflexes, were antagonized partially by Ro 15-1788. When the antagonist was given after high doses of flurazepam, convulsions were produced. Calculation of the likely membrane concentrations of the benzodiazepines showed that these fitted the lipid solubility correlation for general anaesthesia. Ro 15-1788 did not decrease the lethal effects of the benzodiazepines. With flurazepam, chlordiazepoxide and diazepam it caused signs of hyperexcitability, which in the case of flurazepam led to the death of the animals.
为了确定几种苯二氮䓬类药物“全麻”剂量后的苯二氮䓬类拮抗剂Ro 15 - 1788（20毫克/千克）的作用是否归因于其对苯二氮䓬受体的作用，在小鼠中进行了研究。使用雄性CDI小鼠，麻醉终点为翻正反射消失和足趾夹捏反射消失。咪达唑仑以及程度较轻的氯氮䓬和地西泮对这些反射的作用被Ro 15 - 1788部分拮抗。当拮抗剂在高剂量氟西泮给药后给予时，会产生惊厥。苯二氮䓬类药物可能的膜浓度计算表明，这些符合全身麻醉的脂溶性相关性。Ro 15 - 1788并未降低苯二氮䓬类药物的致死作用。对于氟西泮、氯氮䓬和地西泮，它会引起过度兴奋的迹象，在氟西泮的情况下会导致动物死亡。
