Deuterium oxide and inhalation anesthetics.

麻醉剂从膜和蛋白质的界面释放水合水分子。麻醉剂引起的水的结构变化被认为是麻醉的机制。重水中的重水使水的水化作用增强，改变了水的结构。然而，在生物系统中，D_2O对麻醉效力的影响尚未见报道。本实验采用饮水灌胃2周(慢性实验)和急性灌胃生理盐水D_2O溶液灌胃(急性实验)两种方法。在慢性和急性实验中，D_2O均降低吸入麻醉药(异氟醚)的最低肺泡浓度(MAC)，并增加异氟醚的麻醉效力。此外，D_2O还表现出类麻醉性作用，如翻正反射消失、镇痛等。从核磁共振研究中，我们发现醇类化合物的麻醉效力与醇类化合物周围的水合水的数量有关。D_2O增强麻醉作用的机制是：1)D_2O通过增加麻醉剂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具有麻醉剂样作用，D_2O还能增加异氟醚的麻醉效力；3)D_2O影响麻醉剂与膜和蛋白质的结合，改变麻醉药在生物系统中的分布。

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.