Korkmaz S, Ljungblad E, Wahlström G
Department of Pharmacology, Umeå University, Sweden.
Brain Res. 1995 Apr 10;676(2):371-7. doi: 10.1016/0006-8993(95)00132-a.
Interaction between flumazenil, a substance regarded mainly as a benzodiazepine antagonist, and an intravenous anesthetic barbiturate, hexobarbital, was investigated by using an electroencephalography threshold test in male rats. Flumazenil 10 mg/kg given as pretreatment reduced the threshold dose of hexobarbital approximately 20% indicating a synergistic interaction. Similar effects were obtained with the agonists, diazepam 20 mg/kg and lorazepam 2 mg/kg. Dose-response curve for flumazenil (2.5-10 mg/kg) was determined with the same technique and hexobarbital concentrations were analysed in serum and several brain regions at the threshold by high pressure liquid chromatography. Flumazenil 10 mg/kg pretreated group showed a different pattern of distribution of hexobarbital into the tested brain regions indicating a pharmacokinetic interaction. Low concentrations of hexobarbital in the brainstem which were negatively correlated with the dose of flumazenil indicate a pharmacodynamic interaction which could be due to partial agonistic intrinsic activity of flumazenil, usually seen at much higher doses.
通过在雄性大鼠中使用脑电图阈值测试，研究了主要被视为苯二氮䓬拮抗剂的氟马西尼与静脉麻醉性巴比妥酸盐己巴比妥之间的相互作用。预处理给予10mg/kg的氟马西尼可使己巴比妥的阈值剂量降低约20%，表明存在协同相互作用。给予激动剂地西泮20mg/kg和劳拉西泮2mg/kg也获得了类似的效果。采用相同技术测定了氟马西尼（2.5-10mg/kg）的剂量-反应曲线，并通过高压液相色谱法在阈值时分析了血清和几个脑区中的己巴比妥浓度。预处理给予10mg/kg氟马西尼的组显示己巴比妥在受试脑区中的分布模式不同，表明存在药代动力学相互作用。脑干中低浓度的己巴比妥与氟马西尼剂量呈负相关，表明存在药效学相互作用，这可能是由于氟马西尼通常在高得多的剂量下才出现的部分激动剂内在活性所致。
