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DOI 10.1016/j.taap.2006.08.003
Title A proposed mechanism for amitriptyline neurotoxicity based on its detergent nature
Creator/Author Kitagawa, Norihito [Department of Anesthesiology, Tsuruta Orthopedic Clinic, Ushizu, Saga 849-0306 (Japan)]. E-mail: kitagawa@mail.anes.saga-med.ac.jp ; Oda, Mayuko [Analytical Research Center for Experimental Sciences, Saga University, Nabeshima, Saga (Japan)] ; Nobutaka, I. [Department of Clinical laboratory, Saga Medical School, Nabeshima, Saga (Japan)] ; Satoh, Hidetoshi [Saga Medical School Hospital, Saga Medical School, Nabeshima, Saga (Japan)] ; Totoki, Tadahide [Saga Medical School Hospital, Saga Medical School, Nabeshima, Saga (Japan)] ; Morimoto, Masatoshi [Analytical Research Center for Experimental Sciences, Saga University, Nabeshima, Saga (Japan)]
Publication Date2006 Nov 15
OSTI IdentifierOSTI ID: 20850482
Other Number(s)Journal ID: ISSN 0041-008X; TXAPA9; TRN: US07R1744020944
Resource TypeJournal Article
Resource RelationJournal: Toxicology and Applied Pharmacology; Journal Volume: 217; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2006.08.003; PII: S0041-008X(06)00269-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Subject60 APPLIED LIFE SCIENCES; AGGLOMERATION; ANESTHESIA; ANESTHETICS; DETERGENTS; ERYTHROCYTES; HEMOLYSIS; INJURIES; LIPIDS; MEMBRANES; RATS; STIMULI
Description/Abstract Although amitriptyline has gained attention as a potent local anesthetic, recent animal studies showed that it can cause irreversible neural impairment. We hypothesized that nerve membrane disruption caused by solubilization, a common detergent property, accounted for amitriptyline neurotoxicity. We used a two-phase approach to test our hypothesis. Firstly, we determined (1) the molecular aggregation concentration of amitriptyline (2) the concentration of amitriptyline that disrupts artificial lipid membranes and (3) the concentration of amitriptyline that causes hemolysis. Secondly, we compared these levels with neurotoxic concentrations determined from assessment in a rat model of spinal anesthesia using changes in cutaneous stimulus threshold (CST). Amitriptyline concentrations that caused molecular aggregation, model membrane disruption and hemolysis were 0.46%, 0.35% and 0.3%, respectively. Animal study showed a significant increase in CST at {>=} 0.3% of amitriptyline, indicating neurological impairment. Since amitriptyline caused model membrane disruption and hemolysis at the molecular aggregation concentration, solubilization plays a role in the destruction of artificial membranes and erythrocytes. Furthermore, these concentrations are also in good agreement with the minimum concentration causing neurological injury. Therefore, while additional studies, including histopathology, are necessary to clarify this observation, amitriptyline neurotoxicity appears to be associated with its detergent nature.
Country of PublicationUnited States
LanguageEnglish
FormatSize: page(s) 100-106
System Entry Date2007 Apr 02

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