在ddY小鼠中，高剂量氟马西尼可增强丙泊酚的催眠活性，但不能增强硫喷妥钠的催眠活性。

High-dose flumazenil potentiates the hypnotic activity of propofol, but not that of thiopental, in ddY mice.

作者信息

Adachi Y U, Watanabe K, Higuchi H, Satoh T

机构信息

Department of Anesthesiology, National Defense Medical College, Tokorozawa, Saitama, Japan.

出版信息

Acta Anaesthesiol Scand. 2001 Aug;45(7):848-52. doi: 10.1034/j.1399-6576.2001.045007848.x.

DOI:10.1034/j.1399-6576.2001.045007848.x

PMID:11472286

Abstract

BACKGROUND

Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high dose. This study investigated the effects of flumazenil and midazolam on the hypnotic dose of propofol and thiopental in ddY mice, using a behavioral model.

METHODS

Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay.

RESULTS

Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the hypnotic dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P<0.05), but not that of thiopental (9.1+/-0.30 [8.5-9.7] with 0.2 mg kg(-1) flumazenil vs. 9.3+/-0.42 [8.4-10.1] mg kg(-1) with saline). Midazolam reduced the hypnotic dose of both propofol and thiopental. Flumazenil antagonized the potentiating effect of midazolam (0.2 mg kg(-1)) on the hypnotic activity of propofol.

CONCLUSIONS

These results suggest that the hypnotic activity of propofol is potentiated by the partial agonist activity of flumazenil in ddY mice.

摘要

背景

氟马西尼是一种特异性苯二氮䓬类激动剂，据报道在高剂量时具有部分苯二氮䓬类激动剂样效应。本研究使用行为学模型，探讨了氟马西尼和咪达唑仑对ddY小鼠丙泊酚和硫喷妥钠催眠剂量的影响。

方法

给小鼠静脉注射丙泊酚或硫喷妥钠以诱导催眠，催眠定义为翻正反射消失。小鼠预先接受氟马西尼（0.05、0.1或0.2mg kg⁻¹）或咪达唑仑（0.1或0.2mg kg⁻¹）预处理，30秒后给予丙泊酚或硫喷妥钠。

结果

与对照组相比，氟马西尼（0.1或0.2mg kg⁻¹）预处理显著降低了丙泊酚的催眠剂量（9.3±0.39 [8.5 - 10.0]或9.0±0.28 [8.5 - 9.6] vs. 10.8±0.42 [9.9 - 11.6]mg kg⁻¹（半数有效剂量±标准误和[95%置信区间]），P<0.05），但对硫喷妥钠的催眠剂量无影响（0.2mg kg⁻¹氟马西尼时为9.1±0.30 [8.5 - 9.7] vs. 生理盐水时为9.3±0.42 [8.4 - 10.1]mg kg⁻¹）。咪达唑仑降低了丙泊酚和硫喷妥钠的催眠剂量。氟马西尼拮抗了咪达唑仑（0.2mg kg⁻¹）对丙泊酚催眠活性的增强作用。