Kissin I, Brown P T, Bradley E L
Department of Anesthesiology, School of Medicine, University of Alabama, Birmingham 35294.
Anesth Analg. 1990 Sep;71(3):236-41.
The anesthetic effects of morphine-diazepam and fentanyl-diazepam combinations as characterized by abolition of the movement response to noxious stimulation were studied in rats to test the hypothesis of antagonistic interactions between the components of these combinations. Noxious pressure on the tail was used to induce the response. Dose-effect curves were constructed for the drugs given alone and in combination. With the use of probit procedure ED50 values for single drugs and their combinations were determined, and the interactions were analyzed with algebraic (fractional) and isobolographic methods. It was found that both morphine and fentanyl have a less than additive (antagonistic) interaction with diazepam. In combination the sum of fractional doses was higher than a single-drug fractional dose, 1.67 versus 1.00 (P less than 0.05) for morphine-diazepam and 1.61 versus 1.00 (P less than 0.05) for fentanyl-diazepam. The observed antagonism is a relative one that does not increase the requirement for one agent upon the addition of another agent.
为检验吗啡 - 地西泮和芬太尼 - 地西泮组合成分间存在拮抗相互作用这一假说，研究了以消除对有害刺激的运动反应为特征的这些组合的麻醉效果。用对大鼠尾巴施加有害压力来诱发反应。构建了单独给药及联合给药的剂量 - 效应曲线。使用概率单位法确定单一药物及其组合的半数有效剂量（ED50）值，并采用代数（分数）法和等效应线图法分析相互作用。结果发现，吗啡和芬太尼与地西泮均存在小于相加（拮抗）的相互作用。联合用药时，分数剂量之和高于单一药物的分数剂量，吗啡 - 地西泮组合为1.67比1.00（P < 0.05），芬太尼 - 地西泮组合为1.61比1.00（P < 0.05）。观察到的拮抗作用是相对的，在添加另一种药物时不会增加对一种药物的需求量。
