在小鼠模型中对氟马西尼拮抗γ-羟基丁酸酯中毒的研究。
An investigation of flumazenil to antagonize gamma-hydroxybutyrate intoxication in a murine model.
作者信息
Lee David C, Satz Wayne A, Dougherty Timothy, Greene Tucker
机构信息
Department of Emergency Medicine, Drexel University/Medical College of Pennsylvania, PA, USA.
出版信息
J Med Toxicol. 2006 Jun;2(2):68-70. doi: 10.1007/BF03161174.
OBJECTIVE
Prior animal studies have suggested that flumazenil may blunt GHB's sedative-hypnotic affects. We hypothesized that flumazenil would decrease the affects of GHB in a murine model of intoxication.
METHODS
We performed a controlled, pilot experiment using 32 mice divided into 3 groups. All mice received intraperitoneal injections of GHB (1.5 g/kg). Group I received sham injections at time 0, and then GHB at 5 minutes. Group II received flumazenil (0.3 mg/kg) at time 0, and then GHB at 5 minutes. Group III received sham injection at time 0, then GHB at 5 minutes, and then 4 escalating flumazenil doses administered at 3-minute intervals (0.003 to 1 mg/kg). We measured certain functions: time to loss/recovery of righting reflexes (RR), time to sprawl/recovery of sprawl (postural tone [PT]), and death.
RESULTS
There were statistically significant delays in the loss of PT and shortened recovery time to RR in pre-treated mice (group II) versus controls (group I). There were no differences in group III versus group I for any outcome parameters.
CONCLUSIONS
In this model, pre-dosing flumazenil prior to GHB administration delayed clinical intoxication.
目的
先前的动物研究表明，氟马西尼可能会减弱γ-羟基丁酸（GHB）的镇静催眠作用。我们假设氟马西尼会在小鼠中毒模型中降低GHB的作用。
方法
我们进行了一项对照性的初步实验，使用32只小鼠，分为3组。所有小鼠均接受腹腔注射GHB（1.5 g/kg）。第一组在0分钟时接受假注射，然后在5分钟时注射GHB。第二组在0分钟时接受氟马西尼（0.3 mg/kg）注射，然后在5分钟时注射GHB。第三组在0分钟时接受假注射，然后在5分钟时注射GHB，随后每隔3分钟给予4次递增剂量的氟马西尼（0.003至1 mg/kg）。我们测量了某些功能：翻正反射丧失/恢复的时间（RR）、伸展/伸展恢复的时间（姿势张力[PT]）以及死亡情况。
结果
与对照组（第一组）相比，预处理小鼠（第二组）的PT丧失出现统计学上的显著延迟，RR恢复时间缩短。第三组与第一组在任何结局参数上均无差异。
结论
在该模型中，在给予GHB之前预先给予氟马西尼可延迟临床中毒。
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