The interaction between Mammalian Alkaloids and Anesthetics : Anesthetic Tolerance Associated with Alcohol Drinking and Prediction by Hair Analysis
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Asahi University|
TSUCHIYA Hironori Asahi University, School of Dentistry, Professor, 歯学部, 教授 (30131113)
MIZOGAMI Maki Asahi University, School of Dentistry, Associate Professor, 歯学部, 助教授 (10231614)
NAGAYAMA Motohiko Asahi University, School of Dentistry, Lecturer, 歯学部, 講師 (50298436)
|Project Period (FY)
2003 – 2005
Completed(Fiscal Year 2005)
|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 2005 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2004 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 2003 : ¥1,300,000 (Direct Cost : ¥1,300,000)
|Keywords||Anesthetics / Drinking / Decreased Effects / Interaction / Beta-carbolines / Membrane Fluidization / Hair Analysis / Pharmacological Mechanism / β-カルボリンアルカロイド / 膜流動性 / 生体膜マイクロドメイン / 立体異性体 / コレステロール / 生体膜流動性 / リポソーム / 麻酔効果減弱 / 膜流動性変化 / 局所・全身麻酔薬 / 哺乳類アルカロイド|
Concerning anesthetic tolerance associated with drinking, the pharmacological background and prediction method were studied with focusing on the interaction with mammalian alkaloidal β-carbolines. A series of results were applied to various investigations on anesthetic effect change and biomembrane-drug interaction.
1.Certain β-carbolines acted on membrane lipids to inhibit the membrane fluidization by local and general anesthetics. Such inhibition disappeared by their hepatic hydroxylation metabolism. It is speculated that anesthetic effects are decreased by the interaction with membrane-active β-carbolines increased in vivo by drinking.
2.In the newly developed HPLC, the β-carboline concentrations in human scalp hair were found to significantly increase in chronic alcoholics. The potent interaction with β-carbolines to influence anesthesia may be predicted by hair analysis.
3.Local anesthetics showed the reversed-phase chromatographic retention and membrane-fluidizing activity relations
hips. Based on the hydrophobic interaction underlying membrane fluidization, the changes in anesthetic effects are simulated by HPLC analysis.
4.The hydrophobic interaction of local anesthetics was applied to infusion balloons, which adsorbed local anesthetics immediately after injection to decrease their concentrations in effluents. Attention should be given to such adsorption so as not to influence clinical effects.
5.The membrane-fluidizing effects of local anesthetics were induced under inflammatory acidic conditions and inhibited by inflammatory peroxynitrite, conflicting with the conventional hypothesis. The alternative mechanism should be theorized for the anesthetic failure in inflamed tissues.
6.Nerve cell model membranes were fluidized by lidocaine ionic quaternary ammonium derivative and stereostructure-specifically fluidized by S(-)-,R(+)- and racemic bupivacaine and ropivacaine. The interaction with membrane lipids is responsible for the effects of local anesthetics in addition to that with ion channel/receptor proteins.
7.Anesthetic-relating drugs, including new selective β-blockers and phenolic agents, showed the structure-selective membrane-activity, suggesting that the modification of membrane fluidity mechanistically contributes to their effects. Less
Research Products (19results)