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Neurotoxicity Of Tricyclic Antidepresssnats.

Bravoncius Roxford

Bluelighter
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Feb 1, 2017
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Interesting study. All tricyclic antidepressants caused apoptic neuron death in cell cultures. https://www.ncbi.nlm.nih.gov/pubmed/17437653 It's crazy that these drugs, which destroy brain cells and cause early dementia, are freely prescribed. I guess if you suffer from serious depression it might be worth it since if you take a gun to your head and blow your brains out you lose all bran cells. But still, considering that these are brain-tissue destroying molecules, they should be saved as a last resort.
 
i dont see tianeptine in that table. isnt it also a tricyclic antidepressant??
 
All tryciclic antidepressents, which were tested in this study showed neurotoxic potential in the following order: desipramine < amitriptyline < N-methyl amitriptyline < doxepin < trimipramine < imipramine < N-methyl doxepin < N-propyl doxepin. It was tested on rats... Sometimes neurodegeneration can be better in the long run than having a bad functioning brain. Living the rest of your life in despair vs. losing some years, but enjoy your live - I know that I would pick the enjoy your live option.
 
The mechanism of this neurotoxic effect is not known and the authors of this research could not correlate the magnitude of neurotoxicity with action at any specific target, thus until we see similar results for newer antidepressants one can't say that by choosing to accept antidepressant treatment you're choosing to trade some of your cognitive abilities.

Tricyclic antidepressants constitute an old class of antidepressants which should not be a first-line choice for treating depression. TCA's are very unselective SNRI's, aside from SERT and NET inhibition they act on numerous other targets including DAT, 5-HT, DA, adrenergic, histamine, and acetylcholine receptors, some of these actions may add a sedative or anxiolytic component but primarily they are responsible for additional side effects, higher toxicity, and lower therapeutic index of TCA's.

A common trend in all groups of medications is that newer generations are designed to be more selective towards specific target(s) and thus should be safer.

If you look at pharmacodynamic profiles of newer antidepressants (SSRI's, SNRI's etc.), they generally exhibit good selectivity for SERT and/or NET and their affinity at secondary targets is low enough to be considered insignificant in most cases. Some newer antidepressants are designed to act on both SERT and/or NET and other receptors through which its therapeutic effect is increased (e.g. 5-HT1A agonism), but this is done in such a way that they are selective for those selected targets.

asecin said:
i dont see tianeptine in that table. isnt it also a tricyclic antidepressant??

Technically it is a tricyclic compound, but it's structurally different from TCA's and has a different mode of action, so it doesn't fall into the group of TCA's.
 
I can comment on this. I've gone through 10gs of tianeptine sodium over a month. Doses of 125mg 3-4 times a day. Tianeptine behaves more like a weak mu and serotonin agonist rather than anything else, at the dosage I tried it. Like 12.5mg pills would be comparable to placebo, 0desmethyltramadol would be a much better and pleasant experience.
 
Brav, I see you're still on the anti SSRI/TCA tirade.

SSRIs/TCAs as a whole tend to encourage an increase in brain volume, especially hippocampal hypertrophy, and tend to increase the amount of connections between neurons and the strength of connections between neurons.

We can't tunnel vision on what happens in a petri dish. Its much more helpful to look at whole brain experiments/studies. Just because there is some cytotoxicity/increased apoptosis of dorsal root ganglion cells at whatever concentration in vitro doesn't mean that that effect is appreciable to various other neuron types in vivo. It could be especially irrelevant with regards to the pathology that the drugs are attempting to treat.

With regards to the study, here is a study showing that amitriptyline can be protective of dorsal root ganglion cells if the dosage doesn't get too high
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863790/

"Amitriptyline stimulated DRG neuronal development in dose-dependent manner, but exerted toxic effect at concentrations higher than 10?M.

AM reduced lidocaine-induced DRG neurodegeneration by regenerating neurites and growth cones."

Dosage makes the cure or the poison. See this graph and the stains.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863790/figure/F1/

Keep in mind that the dosage/concentration can be pushed incredibly high in vitro to produce effects that will never been seen in vivo.
 
Brav, I see you're still on the anti SSRI/TCA tirade.

SSRIs/TCAs as a whole tend to encourage an increase in brain volume, especially hippocampal hypertrophy, and tend to increase the amount of connections between neurons and the strength of connections between neurons.

We can't tunnel vision on what happens in a petri dish. Its much more helpful to look at whole brain experiments/studies. Just because there is some cytotoxicity/increased apoptosis of dorsal root ganglion cells at whatever concentration in vitro doesn't mean that that effect is appreciable to various other neuron types in vivo. It could be especially irrelevant with regards to the pathology that the drugs are attempting to treat.

With regards to the study, here is a study showing that amitriptyline can be protective of dorsal root ganglion cells if the dosage doesn't get too high
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863790/

"Amitriptyline stimulated DRG neuronal development in dose-dependent manner, but exerted toxic effect at concentrations higher than 10?M.

AM reduced lidocaine-induced DRG neurodegeneration by regenerating neurites and growth cones."

Dosage makes the cure or the poison. See this graph and the stains.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863790/figure/F1/

Keep in mind that the dosage/concentration can be pushed incredibly high in vitro to produce effects that will never been seen in vivo.

Thank you dear brother. I hope you know about the protective power of selenium.
 
I can comment on this. I've gone through 10gs of tianeptine sodium over a month. Doses of 125mg 3-4 times a day. Tianeptine behaves more like a weak mu and serotonin agonist rather than anything else, at the dosage I tried it. Like 12.5mg pills would be comparable to placebo, 0desmethyltramadol would be a much better and pleasant experience.

tramadol does feel similar but i dont think its better. it makes me weak in the knees and its more of a painkiller but it did help with depression issues just in a different way
 
Mate use paroxetine and opipramol for your depression, tramadol is a painkiller.
 
paroxetine is garbage. any SSRI is crap. ill do st jonh's wort and feel it better in a week than any SSRI. ive never heard of opipramol though, is this one widely available in the US??
 
paroxetine is garbage. any SSRI is crap. ill do st jonh's wort and feel it better in a week than any SSRI. ive never heard of opipramol though, is this one widely available in the US??

Wow. Yeah. I don't know where to begin. Let's agree to disagree. Ask your doctor about opipramol.
 
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