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Hello everybody,

I'm thinking of trying Tianeptine, since a few people report that it helped them and it seems to have no serious side effects at all. Tianeptine seems to be an NMDA-modulator, but I'm not so sure what that actually means, and even after reading some studies, I still don't know whether it's an NMDA agonist or antagonist. (One guy on reddit wrote that it's neither an agonist nor an antagonist, but he didn't reference any literature and I didn't really understand his explanation.)

If it's an antagonist, I don't think people with DP/DR should take it, since NMDA antagonists (like Ketamine or alcohol) induce DP/DR.

Maybe somebody knows more about Tianeptine and its effect on the glutamate system/NMDA receptors? Or has any personal experiences with Tianeptine?

Thanks! :)
 

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It's main mechanism of action appears to be activating μ-opioid-receptors in a special kind of way. Whatever it might do on the glutamate system probably isn't significant enough to explain any of it's effects.
 

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Most neurons in the human brain operate with glutamate. You would expect pretty strong effects if Tianeptine really did something significant in this area.
I am not sure I understand. It seems to me you are saying that it has an effect, but it's probably not due to an effect on the glutamate system because if it had an effect on the glutamate system it would have a strong effect. But doesn't the strength of the effect also depend on dosage? I am pretty sure that if you change the dosage you could find one where almost nothing happens and one where you would die of an overdose. So would you care to elaborate? Or are you talking about specific strong effects that you are expecting?
 

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But doesn't the strength of the effect also depend on dosage? I am pretty sure that if you change the dosage you could find one where almost nothing happens and one where you would die of an overdose.
Of course it depends on the dosage. You can even overdose on water and die. But the bottom line is that the mechanism of action of a drug obviously only matters in the dose range you can take without risking your life.
 

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Of course it depends on the dosage. You can even overdose on water and die. But the bottom line is that the mechanism of action of a drug obviously only matters in the dose range you can take without risking your life.
But so I don't understand how you can conclude something from the strength of the effects if the effects can be tuned anyway using the dosage. Like Risperidone has a much stronger effect than Zyprexa and that's why the basic dosage for Risperidone is 1 mg and it's 10 mg for Zyprexa, so that the pills have the same strength eventually. Also they both have an effect on the dopamine system and still they have different strengths. Or am I missing something?
 

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But so I don't understand how you can conclude something from the strength of the effects if the effects can be tuned anyway using the dosage.
You can't increase the dosage above the maximum, because otherwise you overdose, so only the normal dosage range is relevant. If tianeptine really acted directly and strongly on the glutamate system you would expect effects similar to ketamine or other NMDA-antagonists, which it apparently doesn't have.

I did not fully read the Wikipedia article on it, so I'm not sure if it even directly binds to glutamate receptors. To me it looks like it mainly targets μ-opioid-receptors, which by itself could have antidepressant effects. In fact prior to the invention of the first irreverislbe MAO-inhibitor opioids were used to treat depression.
 
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