Deuterium oxide and inhalation anesthetics.

麻醉剂从膜和蛋白质的界面释放水合水分子。麻醉药对水的结构改变被认为是麻醉的机制。氧化氘（重水：D_2O）增强水化作用，改变水的结构。然而，D_2O对生物系统麻醉效力的影响尚未见报道。在本研究中，我们通过连续2周的饮水（慢性实验）或腹腔输注生理盐水D_2O溶液（急性实验）给小鼠注射D_2O。在慢性和急性实验中，D_2O降低了吸入麻醉剂（异氟烷）的最小肺泡浓度（MAC），增加了异氟烷的麻醉效力。D_2O表现出类似麻醉的作用，如翻正反射消失和镇痛。通过核磁共振研究，我们发现醇的麻醉效力与醇分子周围水合水的数量有关。D_2O增强麻醉的机制如下：1)D_2O通过增加麻醉药周围水合水分子的数量来增强麻醉药的药理作用。2)由于D_2O具有类麻醉作用，D_2O可加性地提高异氟醚的麻醉效力。3) D_2O影响麻醉药物与膜和蛋白质的结合，改变麻醉药物在生物系统中的分布。目前的研究结果表明，水分子的结构变化与麻醉有关。

Anesthetics release the hydration water molecule from the interface of membranes and proteins. The structure change of water by anesthetics has been proposed to be the mechanism of anesthesia. Deuterium oxide (heavy water : D_2O) potentiates the hydration, and changes the water structure. However, the effects of D_2O on the anesthetic potency in biological system have never been reported. In this study, we gave D_2O to mouse by drinking water for 2 weeks (chronic experiment), or by peritoneal infusion of physiological saline D_2O solution (acute experiment). Both in chronic and acute experiments, D_2O decreased MAC (minimum alveolar concentration) of inhalation anesthetics (isoflurane), and increased the anesthetic potency of isoflurane. Furthermore, D_2O showed the anesthesia-like effects, such as disappearance of righting reflex and analgesia. From NMR study, we found that the anesthetic potency of alcohols correlates to the number of hydration water around alcohol molccule. The mechanisms of potentiation of anesthesia by D_2O were the followings :1) D_2O potentiate the pharmacological efficacy of anesthetics by increasing number of hydration water molecule around anesthetics.2) Because D_2O has the anesthetic-like effect, D_2O increases the anesthetic potency of isoflurane, additively.3) D_2O affects anesthetic binding to membranes and proteins, and changes the distribution of anesthetics in biological system.The present results indicate that the structure change of water molccule relates to anesthesia.