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How does tianeptine increase the risk of serotonin syndrome (in combination)

"Lower serotonin" is quite ambiguous. As far as I know, tianeptine decreases extracellular concentrations of 5-HT by enhancing reuptake, but this doesn't necessarily mean that 5-HT is, overall, "lowered."
 
I don't think it is directly enhancing uptake at the serotonin transporter. To say that it increases excitatory post synaptic currents at serotonergic neurons seems to make more sense.

"The enhancement of EPSCs could be blocked by the intracellular presence of the kinase inhibitor staurosporine (1 micro m), suggesting the involvement of a postsynaptic phosphorylation cascade rather then presynaptic release mechanisms at CA3 c/a synapses. These results indicate that tianeptine targets the phosphorylation-state of glutamate receptors at the CA3 c/a synapse"

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12372016&ordinalpos=12&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
 
Does tianeptine increase the risk of Serotonin syndrome? I have not heard of that before, to be honest.

Tianeptine is quite lovely, IMO. It comes close after K as a wonder-drug ;).
 
Interestingly, both tianeptine (reuptake enhancer) and SSRIs increase neurogenesis, paradoxical considering you might expect oppositional effects.

Maybe the reason for some sort of syndrome is that the compensatory mechanisms that occur on a localized level rather than the net effect, mean that compensatory mechanisms are working in both directions at once, causing some sort of serotonin meltdown perhaps? idk.
 
I am not sure anyone really knows why Tianeptine works as it does, but many love it
as an SSRE it is in a class by itself
I am sure many o big pharma are trying to unlock this puzzle
 
It is one of the best cures for an ecstasy comedown (which actually makes sense - it puts all that synaptic serotonin back inside the cells it was released from). It is also the only antidepressant that ever did anything positive for me.

As well, it has absolutely no negative side-effects.
 
Ah That paper with the increase in excitatory synaptic traffic is really a bit unrelated, seeing as it is in the hippocampus.

However, tianeptine does increase BDNF release in the amygdala [1] which is a far more likely mechanism.

Meanwhile, I can't find a single reference to the idea that tianeptine can cause serotonin syndrome in the published literature.

Indeed, the evidence that tianeptine decreases serotonin release is actually really thin on the ground [2].
 
I can't find a single reference to the idea that tianeptine can cause serotonin syndrome in the published literature.
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a while ago i was looking if tianeptine could be a cure for serotonin sxndrome but instead found a fey reports of it caug#sing it when used in combination with other drugs
il look them up again when im back home

It is one of the best cures for an ecstasy comedown (which actually makes sense - it puts all that synaptic serotonin back inside the cells it was released from). It is also the only antidepressant that ever did anything positive for me.

As well, it has absolutely no negative side-effects.
Click to expand...
it makes alot sense indeed, there also is a report of it potentiating mdma wich makes sense too but i dont know the danger of doing that
 
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