Interaction of Local Anesthetics with Biomembranes Consisting of Phospholipids and Cholesterol: Mechanistic and Clinical Implications for Anesthetic and Cardiotoxic Effects
| Autor: | Tsuchiya, Hironori, Mizogami, Maki, Department of Dental Basic Education, Asahi University School of Dentistry, 2Department of Anesthesiology and Reanimatology, University of Fukui Faculty of Medical Sciences |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
business.industry
Cholesterol Sodium channel Membrane lipids Review Article Pharmacology Critical Care and Intensive Care Medicine Transmembrane protein lcsh:RD78.3-87.3 chemistry.chemical_compound Anesthesiology and Pain Medicine Membrane chemistry lcsh:Anesthesiology Amphiphile Anesthetic Biophysics Medicine business Lipid bilayer medicine.drug |
| Zdroj: | Anesthesiology Research and Practice Anesthesiology Research and Practice, Vol 2013 (2013) |
| ISSN: | 1687-6970 1687-6962 |
| Popis: | Despite a long history in medical and dental application, the molecular mechanism and precise site of action are still arguable for local anesthetics. Their effects are considered to be induced by acting on functional proteins, on membrane lipids, or on both. Local anesthetics primarily interact with sodium channels embedded in cell membranes to reduce the excitability of nerve cells and cardiomyocytes or produce a malfunction of the cardiovascular system. However, the membrane protein-interacting theory cannot explain all of the pharmacological and toxicological features of local anesthetics. The administered drug molecules must diffuse through the lipid barriers of nerve sheaths and penetrate into or across the lipid bilayers of cell membranes to reach the acting site on transmembrane proteins. Amphiphilic local anesthetics interact hydrophobically and electrostatically with lipid bilayers and modify their physicochemical property, with the direct inhibition of membrane functions, and with the resultant alteration of the membrane lipid environments surrounding transmembrane proteins and the subsequent protein conformational change, leading to the inhibition of channel functions. We review recent studies on the interaction of local anesthetics with biomembranes consisting of phospholipids and cholesterol. Understanding the membrane interactivity of local anesthetics would provide novel insights into their anesthetic and cardiotoxic effects. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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