Deuterium oxide and inhalation anesthetics.

氧化氘和吸入麻醉剂。

• 批准号: 05671261
• 负责人: MASHIMO Takashi
• 金额: $ 1.34万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671261/
• 关键词: Deitium Oxide; Isoflurane; MAC

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.

麻醉剂从膜和蛋白质的界面释放水合水分子。麻醉剂改变水的结构被认为是麻醉的机理。氧化氘（重水：D_2O）的加入，增强了水化作用，改变了水的结构。然而，D_2O对生物系统麻醉效能的影响尚未见报道。本研究采用饮水给药法（慢性实验）和腹腔注射生理盐水给药法（急性实验），对小鼠进行了D_2O染毒。在慢性和急性实验中，D_2O均使吸入麻醉药（异氟醚）的最低肺泡浓度（MAC）降低，并使异氟醚的麻醉强度增加。此外，D_2O还表现出翻正反射消失、镇痛等麻醉样作用。通过核磁共振研究发现，醇类物质的麻醉效力与其分子周围的水化程度有关。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目而增强麻醉剂的药理作用;（2）由于D_2O具有麻醉样作用，D_2O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，改变麻醉剂在生物系统中的分布。

项目成果

上農喜朗 他4人: "麻酔作用と重水:マウスにおけるインフルレンMACに対する重水の効果" The Jeurnal of Deutrium Science. 3. 15-17 (1993)

Yoshiro Kamino 和其他 4 人：“麻醉作用和重水：重水对小鼠流感 MAC 的影响”《氘科学杂志》，3. 15-17 (1993)。

Tomoyoshi Seto,et al.: "Contribution of hydration water to anesthetic potency : NMR studies on molecular motion of hydration water in alcohol-D20 solution." Progress in Anesthetic Mechanism 3 (Special Issue). 3. 380-384 (1995)

Tomoyoshi Seto 等人：“水合水对麻醉效力的贡献：醇-D20 溶液中水合水分子运动的 NMR 研究。”

瀬戸倫義他2名: "アルコール重水水溶液中における水和水の動的構造" The Journal of Deutrium Science. 4. 48-50 (1994)

Michiyoshi Seto 等人 2：“醇重水溶液中水合水的动态结构”，氘科学杂志，4. 48-50 (1994)。

Tomoyoshi Seto,et al.: "Contribution of hydration water to anesthetic potency-NMR studies on molecular motion of hydration water in alcohol-D_2O solution." International Workshop on Anesthetic Mechanisms. 36- (1994)

Tomoyoshi Seto 等人：“水合水对麻醉效力的贡献 - 醇-D_2O 溶液中水合水分子运动的核磁共振研究。”

Yoshiroh Kaminoh, Tomoyoshi Seto, Yuriko Sugiyama, Kiyoshi Yoshikawa and Takashi Mashimo: "Anesthesia and deutrium Oxide : Effects of heavy water on MAC of isoflurane." The Journal of Deutrium Science. 3. 15-17 (1993)

Yoshiroh Kaminoh、Tomoyoshi Seto、Yuriko Sugiyama、Kiyoshi Yoshikawa 和 Takashi Mashimo：“麻醉和氧化氘：重水对异氟醚 MAC 的影响”。