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MDMA &
Empathogenic
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Tianeptine for tolerance reversal? Thoughts please?
- Thread starter VelocideX
- Start date
I've researched tianeptine extensively and I've also imported it and used it for several months. It is an excellent anxyolitic but in my experience the antidepressant effects are over-hyped. Nonetheless, it mellows you out for about 90 min. I don't have experiences with benzodiazepines or other real anti-anxiety medications so I can't offer a comparison, but I can reassure you that it is not a placebo. It has a short half-life of 2.5 hrs so that effect is frustratingly short. True to the hype, however, there are no side-effects.
I've noticed that when I take several pills before I exercise I do not fatigue nearly as quickly and I'm not nauseous after I exercise. This should make sense in light of the emerging hypothesis that tianeptine exerts its primary effects on the glutamate system.
I don't remember where I found this, but you can thank Reagan et al., 2004:
The mechanism by which tianeptine achieves its neuroprotective
and trophic effects, and therefore, its clinical
efficacy, is also unique, since it acts directly by normalizing
glutamatergic transmission.
Furthermore, studies on the expression of the glial
specific excitatory aminoacid transporter GLT1 showed that
they are upregulated in the hippocampal CA3 region and
dentate gyrus, after stress conditions similar to those that
induced dendritic remodeling. This effect was prevented by
tianeptine, demonstrating the role of this antidepressant in
the regulation of stress-induced changes in the glutamatergic
system, perhaps by normalizing synaptic concentrations of
glutamate thus eliminating the stimulus for increased GLT1
expression
I found this somewhere else (sorry for the absence of a citation) :
So far, only fractional indices on the clinical importance of the interaction between glutamate and ACTH secretion have been obtained in both preclinical and clinical studies. Some antidepressant drugs, such as tianeptine, which were found to modulate ACTH release, appear to interfere with brain glutamatergic system. Changes in ACTH and cortisol release may be of importance for mood stabilizing effects of antiepileptic drugs modulating glutamate release, such as lamotrigine.
Tianeptine prevents overstimulation of AMPA/kainate type glutamate receptors in the hippocampus that regulate Ca2+ entry into the nerve cell; excess Ca2+ entry into nerve cells is toxic.
I am really excited about that last part and I would like to probe the experts on this forum about the potential use of tianeptine for attenuating amphetamine tolerance or overstimulation.
I've noticed that when I take several pills before I exercise I do not fatigue nearly as quickly and I'm not nauseous after I exercise. This should make sense in light of the emerging hypothesis that tianeptine exerts its primary effects on the glutamate system.
I don't remember where I found this, but you can thank Reagan et al., 2004:
The mechanism by which tianeptine achieves its neuroprotective
and trophic effects, and therefore, its clinical
efficacy, is also unique, since it acts directly by normalizing
glutamatergic transmission.
Furthermore, studies on the expression of the glial
specific excitatory aminoacid transporter GLT1 showed that
they are upregulated in the hippocampal CA3 region and
dentate gyrus, after stress conditions similar to those that
induced dendritic remodeling. This effect was prevented by
tianeptine, demonstrating the role of this antidepressant in
the regulation of stress-induced changes in the glutamatergic
system, perhaps by normalizing synaptic concentrations of
glutamate thus eliminating the stimulus for increased GLT1
expression
I found this somewhere else (sorry for the absence of a citation) :
So far, only fractional indices on the clinical importance of the interaction between glutamate and ACTH secretion have been obtained in both preclinical and clinical studies. Some antidepressant drugs, such as tianeptine, which were found to modulate ACTH release, appear to interfere with brain glutamatergic system. Changes in ACTH and cortisol release may be of importance for mood stabilizing effects of antiepileptic drugs modulating glutamate release, such as lamotrigine.
Tianeptine prevents overstimulation of AMPA/kainate type glutamate receptors in the hippocampus that regulate Ca2+ entry into the nerve cell; excess Ca2+ entry into nerve cells is toxic.
I am really excited about that last part and I would like to probe the experts on this forum about the potential use of tianeptine for attenuating amphetamine tolerance or overstimulation.
BilZ0r said:
I wanted to send this as a PM but I guess I can't until I've reached a different status. Anywho...
Hi, I really enjoyed your thoughts on the aforementioned subject. I'd like to add a few if you don't mind.
Tianeptine has only been found to cause SERT down-regulation in the dorsal raphe nucleus, and not the median raphe nucleus (KURODA Y. ; WATANABE Y. ; MCEWEN B. S. ; Tianeptine decreases both serotonin transporter mRNA and binding sites in rat brain. http://cat.inist.fr/?aModele=afficheN&cpsidt=4124690).
Now, take a look at this, MDMA only causes toxicity in the dorsal raphe nucleus, but works on both the dorsal raphe nucleus AND the median raphe nucleus (GARTSIDE S. E. (1) ; MCQUADE R. (1) ; SHARP T. (1) , Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on 5-HT cell firing and release : Comparison between dorsal and median raphe 5-HT systems. http://cat.inist.fr/?aModele=afficheN&cpsidt=2151625).
So, even though it is *highly* speculative, it is possible that tianeptine might prevent certain elements of damage from MDMA, while allowing other aspects of the experience through. Or at least, it does not seem like it would totally prevent the effects of MDMA.