Drug Interactions between Sedatives and Analgesics in Rat Cerebral Cortical Synaptoneurosomes, Phospholipids Model Membrane, and Autonomic Nervous Activity

大鼠大脑皮层突触神经小体、磷脂模型膜和自主神经活动中镇静剂和镇痛药之间的药物相互作用

• 批准号: 13672116
• 负责人: KUDO Masaru
• 金额: $ 2.3万
• 依托单位: Health Sciences University of Hokkaido
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672116/
• 关键词: sedative and analgesic; Conscious Sedation; Prolonged sedated state; Postoperative nausea and vomiting; Anxiety; Pain; GABAA receptor complex; 鎮痛剤; 鎮静剤; 薬剤相互作用; 運動機能低下; GABA_Aレセプター; リン脂質二重膜

Presently, we conducted the following general studies using the electroencephalogram and( electrocardiogram real time analysis through observation of the degree of stress and tension in patients, behavioral observation by introducing a behavioral pharmacological observation apparatus, test tubes binding experiments using radioisotopes, quantitative analysis of hormone excretions, with analysis of isatine which is an endogenous nerve active substance having broad biological activities using proton-NMR.・The results of the electroencephalogram revealed that the electroencephalogram component: n-wave (13-30Hz) component increased when both pentazocine and midazolam were given together and extended the sedative state.・Sympathetic nerve activities increased with pentazocine, while midazolam decreased these activities. Therefore, the effects of pentazocine and midazolam on the sympathetic nerves were found to be directly opposite actions.・Parasympathetic nerve activities increased with pentaz … More ocine, but decreased with midazolam.・With injection of an epinephrine-added local anesthetic solution to the oral mucous membrane, the epinephrine level in the adrenal veins decreased, but the epinephrine level increased in the femoral artery.・We found no effects from administration of either analgesics or sedatives in terms of anxiety two hours after sedation was completed.・Nausea, vomiting and dizziness after sedation were exacerbated by administering analgesics.・We could not find a suitable method of administering both sedatives and analgesics to minimize the side effects of both agents.・We developed and synthesized thiazole-coumarin derivatives: 3-(4-chloromethylthiazole-2-y)-7-dimethyl-aminochromen--2-one and 3-(5-acetyl-4-methylthiazole-2-yl)-7-diethylaminochromen-2one, fluorescent derivative forming agents against isatine for high performance liquid chromatography which are applicable as fluorescent derivative forming agents for HPLS when analyzing biological functions and biokinetics.In the future, we would like to concentrate our studies in behavioral observations which can be applied to clinical studies, and to promote collaborative studies combining experiments using the electroencephalogram and electrocardiogram real time analysis with biochemical experiments, in an attempt to contribute our efforts to provide "successful operations, treatments and routine operation management with adequate safety under optimal conditions for both patients and medical care providers in the field of dentistry." Less

目前，我们通过观察患者的应激和紧张程度，使用脑电图和心电图真实的时间分析，通过引入行为药理学观察装置进行行为观察，使用放射性同位素的试管结合实验，激素分泌的定量分析，使用质子-NMR分析靛红，靛红是具有广泛生物活性的内源性神经活性物质。脑电图结果显示，喷他佐辛与咪达唑仑合用时，n波（13- 30 Hz）成分增加，延长了镇静状态。交感神经活动增加喷他佐辛，而咪达唑仑减少这些活动。因此，喷他佐辛和咪达唑仑对交感神经的作用是直接相反的。副交感神经活动增加与pentaz ...更多信息 ocine，但咪达唑仑降低。向口腔粘膜注射添加肾上腺素的局部麻醉溶液后，肾上腺静脉中的肾上腺素水平降低，但股动脉中的肾上腺素水平升高。·我们发现，在镇静完成后两小时，镇痛剂或镇静剂对焦虑没有影响。镇静后的恶心、呕吐和头晕会因服用镇痛药而加重。·我们无法找到一种同时使用镇静剂和镇痛剂的合适方法，以最大限度地减少这两种药物的副作用。·我们开发并合成了噻唑-香豆素衍生物：3-（4-氯甲基噻唑-2-基）-7-二甲基-氨基色烯-2-酮和3-（5-乙酰基-4-甲基噻唑-2-基）-7-二乙氨基色烯-2酮，高效液相色谱法用靛红的荧光衍生物形成剂，在生物功能和生物活性分析时可用作HPLS的荧光衍生物形成剂。我们希望将我们的研究集中在可以应用于临床研究的行为观察上，并促进将使用脑电图和心电图真实的时间分析的实验与生化实验相结合的合作研究，试图为提供“成功的手术，在牙科领域，在患者和医疗护理提供者的最佳条件下，以足够的安全性进行治疗和常规操作管理。“减

项目成果

KUDO MASARU: "Efficacy of nitrous oxide/oxygen inhalation sedation dentistry-providing painless, safe, and comfortable dental treatment-"Medical Gas. 5(1). 21-27 (2003)

工藤胜：“一氧化二氮/氧气吸入镇静牙科的功效——提供无痛、安全、舒适的牙科治疗——”医用气体。

Masaru KUDO, et al.: "Positive correlation between the face anxiety scale and the state anxiety inventory in elderly Dental patients"HIGASHI NIPPON DENTAL JOURNAL. 22・1. 29-33 (2003)

Masaru KUDO 等：“老年牙科患者的面部焦虑量表与状态焦虑量表之间的正相关”《东日本牙科杂志》22・1（2003）。

M.Kudo, H.Ohke, T.Kawai, et al.: "The Relationship Between trait Anxiety and Pain Sensation: Anxiety and Pain levels at puncture and Cannulation in High-Anxiety-State Volunteers"Anesth Prog. 48. 97-98 (2001)

M.Kudo、H.Ohke、T.Kawai 等人：“特质焦虑与疼痛感觉之间的关系：高度焦虑状态志愿者穿刺和插管时的焦虑和疼痛水平”麻醉进展。

工藤 勝: "歯科における亜酸化窒素・酸素吸入鎮静法の有効性-痛くない,安心・快適な歯科医療を目指した笑気吸入鎮静法の有効利用-"Medical Gases. 5・1. 21-27 (2003)

Masaru Kudo：“一氧化二氮/氧气吸入镇静在牙科中的有效性 - 有效使用笑气吸入镇静实现无痛、安全和舒适的牙科护理”《医疗气体》21-27 (2003)。

Naozumi Nichizono, Kazuaki Oda, et al.: "A novel method for the synthesis of 4'-thiopyrimidine nucleoside using hypervalent iodine compounds"Organic Biomolecular Chemistry. 1. 3692-3697 (2003)

Naozumi Nichizono、Kazuaki Oda 等人：“使用超价碘化合物合成 4-硫代嘧啶核苷的新方法”有机生物分子化学。