2005 Fiscal Year Final Research Report Summary
The interaction between Mammalian Alkaloids and Anesthetics : Anesthetic Tolerance Associated with Alcohol Drinking and Prediction by Hair Analysis
| Project/Area Number |
15592145
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Asahi University |
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Principal Investigator |
TSUCHIYA Hironori Asahi University, School of Dentistry, Professor, 歯学部, 教授 (30131113)
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| Co-Investigator(Kenkyū-buntansha) |
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)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Anesthetics / Drinking / Decreased Effects / Interaction / Beta-carbolines / Membrane Fluidization / Hair Analysis / Pharmacological Mechanism |
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| Research Abstract |
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
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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
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Research Products
(11 results)
