Norberg L, Wahlström G
Acta Pharmacol Toxicol (Copenh). 1986 Feb;58(2):96-104. doi: 10.1111/j.1600-0773.1986.tb00077.x.
The anaesthetic interaction between hexobarbital and thiopental in different combinations were investigated in male rats by using the isobolografic method. Data on dose, serum or brain concentrations at an EEG-criterion induced with a threshold method were utilized. The criterion was defined by a burst suppression in the EEG of 1 sec. or more (the "silent second"). With rats more than 115 days of age a synergistic interaction (potentiation) was obtained when a low dose of hexobarbital and a high dose of thiopental were used. The relationship between serum and brain concentrations of hexobarbital and thiopental in the different tested combinations gave no evidence for a pharmacokinetic interaction. Thus the synergistic interaction was located in the brain and probably related to the mechanisms of action. The same tests performed on rats at an age of approximately 90 days gave not only a potentiation when a low dose of hexobarbital and a high dose of thiopental were used, but also a potentiation when a high dose of hexobarbital and a low dose of thiopental were used. These results indicate an age-related change in sensitivity in the CNS between 90 and 115 days of age. Further investigations of this age-related change showed that this change from a potentiation to an additive interaction occurred between the age of 85 and 96 days.
采用等效应线图法，对雄性大鼠不同组合的己巴比妥和硫喷妥钠之间的麻醉相互作用进行了研究。使用阈值法诱导脑电图标准时的剂量、血清或脑浓度数据。该标准定义为脑电图中出现1秒或更长时间的爆发抑制（“沉默秒”）。对于115日龄以上的大鼠，当使用低剂量己巴比妥和高剂量硫喷妥钠时，可获得协同相互作用（增强作用）。在不同测试组合中，己巴比妥和硫喷妥钠的血清浓度与脑浓度之间的关系没有显示出药代动力学相互作用的证据。因此，协同相互作用发生在大脑中，可能与作用机制有关。对约90日龄的大鼠进行相同测试时，不仅使用低剂量己巴比妥和高剂量硫喷妥钠时出现增强作用，而且使用高剂量己巴比妥和低剂量硫喷妥钠时也出现增强作用。这些结果表明，在90至115日龄之间，中枢神经系统的敏感性存在与年龄相关的变化。对这种与年龄相关变化的进一步研究表明，这种从增强作用到相加相互作用的变化发生在85至96日龄之间。
