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Cymbalta's Effect On Nerves


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#1 fishinghat

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Posted 30 June 2020 - 04:39 PM

https://pubmed.ncbi....h.gov/32415528/

 

The induction of nerve cell death by duloxetine was promoted by the CYP inducer rifampicin (an antibiotic used to treat tuberculosis). Lengthening of nerve cell branches was promoted by duloxetine via reduction of the CYP2D6 and MDA levels and induction of Bdnf protein levels. Duloxetine induces neural cell death through effects on CYP and promotes  lengthening of nerve cell branches by regulating CYP, Bdnf protein, and the intracellular lipid peroxidation level.

 

In an in vitro study, CYP2D6 level was inhibited by a very low concentration of duloxetine; in vivo, a CYP1A2 inhibitor caused a significant increase in the Cmax (maximum plasma concentration) of duloxetine, this indicated that both CYP2D6 and CYP1A2 participate in duloxetine metabolism

 

it was stated that duloxetine did not result in any physiological effect on neurogenesis (Marlatt et al. 2010). Duloxetine promoted nerve cell outgrowth of N2a cells by decreasing the intracellular CYP2D6 and MDA levels, and increasing the Bdnf protein levels of intracellular and extracellular. Collectively, these findings revealed that duloxetine is a potential anti-neuroblastoma cell agent and a promoter of neural network reconstruction. Nerve cell death was only observed in the higher duloxetine concentration including less distinct cell boundaries and cell shrinkage. The toxicity of duloxetine was due to the inhibition of cytochrome P450 (CYP) enzyme levels.

 

In clinical studies, after twice daily oral doses of 60 mg, the maximum plasma concentration of duloxetine in adults was 0.48 μM or 144 ng/ml (highest dose studied for efficacy), The neural toxic doses in this study were 100.0 μM,

 

Duloxetine treatment at 20 μM induced human neuroblastoma SH-SY5Y cell death (Engel et al. 2018), whereas this agent showed some protective effect of against oxidative stress–induced cell death following treatment with 1–5 μM (for SH-SY5Y cells) (Engel et al. 2018)





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