A proposed mechanism for amitriptyline neurotoxicity based on its detergent nature

Kitagawa, Norihito; Oda, Mayuko; I, Nobutaka; Satoh, Hidetoshi; Totoki, Tadahide; Morimoto, Masatoshi

doi:10.1016/j.taap.2006.08.003

Cited by 26 publications

(20 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In control cells, we found that oxidized products represented approximately 25%, but after 24 h of amitriptyline treatment the oxidation raised to 75%. This proposal is in agreement with the results of Kitagawa et al (2006) who determined that amitriptyline demonstrates a detergent nature and causes membrane disruption, although they used a significantly higher drug concentration.…”

Section: Discussionsupporting

confidence: 92%

Cytotoxic effects of amitriptyline in human fibroblasts

et al. 2008

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

Cytotoxic effects of amitriptyline in human fibroblasts

et al. 2008

View full text Add to dashboard Cite

“…DTAB is one of the most widely used cationic surfactants in chemical industries (31). Amitripyline is commonly used as an antidepressant, and its detergent properties allow partitioning into lipid bilayers and contribute to its toxicity to mammalian neurons (32). Previous work has already demonstrated that a ⌬MWX strain (in a strain NCIB3610 background) is more highly sensitive to the detergents Triton X-10 and SDS (35).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic and Phenotypic Characterization of aBacillus subtilisStrain without Extracytoplasmic Function σ Factors

et al. 2010

View full text Add to dashboard Cite

Bacillus subtilis encodes seven extracytoplasmic function (ECF) factors. Three ( M , W , and X ) mediate responses to cell envelope-active antibiotics. The functions of V , Y , Z , and YlaC remain largely unknown, and strong inducers of these factors and their regulons have yet to be defined. Here, we define transcriptomic and phenotypic differences under nonstress conditions between a strain carrying deletions in all seven ECF factor genes (the ⌬7ECF mutant), a ⌬MWX triple mutant, and the parental 168 strain. Our results identify >80 genes as at least partially dependent on ECF factors, and as expected, most of these are dependent on M , W , or X , which are active at a significant basal level during growth. Several genes, including the eps operon encoding enzymes for exopolysaccharide (EPS) production, were decreased in expression in the ⌬7ECF mutant but affected less in the ⌬MWX mutant. Consistent with this observation, the ⌬7ECF mutant (but not the ⌬MWX mutant) showed reduced biofilm formation. Extending previous observations, we also note that the ⌬MWX mutant is sensitive to a variety of antibiotics and the ⌬7ECF mutant is either as sensitive as, or slightly more sensitive than, the ⌬MWX strain to these stressors. These findings emphasize the overlapping nature of the seven ECF factor regulons in B. subtilis, confirm that three of these ( M , W , and X ) play the dominant role in conferring intrinsic resistance to antibiotics, and provide initial insights into the roles of the remaining ECF factors.

show abstract

“…Amitriptyline treatment induces alteration of cellular permeability based on its detergent nature (Kitagawa et al, 2006). Furthermore, amitriptyline causes alterations in the glucidic metabolism of neurons resulting in a decrease of both uptake and transport of glucose (Mannerstrom and Tahti, 2004).…”

Section: Amitriptyline As An Anti-cancer Agentmentioning

confidence: 99%