First of all, I do realize that this is an old thread, and I apologize for resurrecting it, but a few of the last posts really kind of irked me..
I am a psychopharmacologist and the founder and director of Oracle Laboratories and NeuroPsych Laboratories, and have been working with Tianeptine and some structurally related compounds in vitro and in vivo human and animal models during the past eight months or so (hence my stumbling across this thread, while browsing “recreational use” Tianeptine threads), so perhaps I can clarify a few points.
Neurotransmitter Reuptake Enhancers work by possessing a binding affinity for the specific neurotransmitter transporter molecule. In the case of Tianeptine, it has long been theorized that Tianeptine’s principal pharmacological mechanism of action is to bind to the Serotonin Transporter (SERT) thereby enhancing the reuptake of serotonin into the pre-synaptic neuron, effectively leading to a decrease in extracellular concentrations of serotonin, and therefore a decrease in serotonin neurotransmission.
However, our research has shown that Tianeptine does not really possess any noteworthy affinity for the Serotonin Transporter, which calls into question it’s “Reuptake Enhancer” action. Examining our EMRI (Electroconductive Magnetic Resonance Imaging) Scanner images, we have not found any evidence that Tianeptine either increases or decreases extracellular concentrations of serotonin in the cortico-limbic structures of the mammalian brain, and Tianeptine did not display any noteworthy long-term effect on the serotonin pathway. Though, Tianeptine does display minor affinity for some of the other monoamine transporters. Our proposed action of Tianeptine on serotonin uptake is that it’s action is indirect, and occurs secondarily, via alteration of AMPA and NMDA glutamate receptor affinity, and by the potentiation of the Hippocampal CA1 pathway.
Using phosphor-florescent-crystallization of target receptors using EMRI Imaging, we have confirmed a direct affinity for the mammalian mu-opioid receptor as well as the delta-opioid receptors in both rodent and human models, and we have confirmed Tianeptine’s action as a moderate-strength agonist of the mu-opioid receptors, and have confirmed a considerably weaker agonist action at the delta opioid receptors. Obviously, this is the only logical action that explains Tianeptine’s opioid-like effects that recreational users experience.
I also want to clarify a few comments made by Psychedelic Jay, including:
This should be really cool to take. It basically does the same thing to serotonin as benzos do to GABA. It simply enhances the way serotonin works, verses SSRI's which just flood the brain with it. I imagine this would give the quasi-opiate like experience due to the sharpness of it's effects, but not anywhere in the same ballpark in prescribed doses.
I really am quite confused by this comment and I feel that others who have posted here are probably confused as well.
Firstly, benzodiazepines do not affect the synaptic or neuronal concentration of GABA at all, nor do they “enhance” the way that GABA works. (As this would require a binding affinity for the GABA transporter, or require an action as a pre-synaptic GABA-releasing agent. - Neither of which any benzodiazepine possesses). Benzos do not have any affect on GABA’s binding affinity for the ionotropic GABA-a receptors, or the metabotropic GABA-b receptors. Nor do benzodiazepines have any affect on synaptic or pre-synaptic neuronal concentrations of GABA.
Benzodiazepines simply mimic GABA and elicit a response from the GABA receptors since benzos possess binding affinity for the GABA receptors (almost solely the ionotropic GABA-a receptors) - specifically, the Benzodiazepine-Binding-Site on the GABA-a receptors. (The same binding site that the “z drugs” bind to, however, distinct from the site where the barbituates and methocarbamates bind to).
An example of a serotonergic drug that affects the Serotonergic System the way that benzodiazepines affect the GABA System would be a 5-HT receptor agonist like Buspirone (name brand Buspar), for example (which functions as a 5-HT1a serotonin receptor agonist, like benzos function as GABA receptor agonists). Like benzodiazepines mimic GABA and elicit a response from the GABA receptors, Buspirone mimics serotonin and elicits a response from the serotonin receptors. Neither have any affect on the neurotransmitters themselves, however.
My point, is that benzodiazepines do not affect GABA’s biosythesis, metabolism, binding affinity, release, reuptake, nor it’s synaptic or pre-synaptic concentrations, as implied by a few of the posts in this thread. - Benzos simply mimic GABA and elicit an agonist response from the GABA receptors like GABA itself does.
As mentioned above, our research has demonstrated that Tianeptine actually does not possess any noteworthy direct action on the Serotonin Transporter, nor does it affect spontaneous firing rates of serotonergic neurons, despite the previous theories that suggested Tianeptine functioned primarily as a Serotonin Reuptake Enhancer, it is worth noting that Tianeptine’s affinity for NMDA glutamate pathways may contribute to it’s perceived action as a drug that decreases extracellular concentrations of serotonin.
In general, Neurotransmitter Reuptake Inhibitors and Neurotransmitter Reuptake Enhancers, specifically relating to depression, both enhance the action of the neurotransmitter in question, although in very different and opposite ways. Reuptake Inhibitors prevent the monoamine transporter in question from reuptaking the neurotransmitter back into the pre-synaptic neuron, thereby flooding the post-synaptic neuron. In contrast, Reuptake Enhancers assist the neurotransmitter transporter, effectively increasing the reuptake of the neurotransmitter in question, back into the pre-synaptic neuron, allowing higher concentrations of the neurotransmitter in question to accumulate in the pre-synaptic neuron, which makes more of that specific neurotransmitter available for neuronal neurotransmission to the receiving, post-synaptic neuron. So, perhaps this is what Psychedelic Jay means by a Serotonin Reuptake Enhancer “enhancing serotonin efficiency”.
No, it doesn't have the same effects as SSRI's.
SSRI's flood the brain, but do not in crease efficiency of serotonin, leading to that dull feeling, and fake wall of happiness.
Tianeptine (Stablon) increases serotonin efficiency by causing the brain to use more of the serotonin properly that is already there, not overloading synapses and dulling uptake like SSRI's
My research into this odd class of drugs has led to the development of a few novel structural relatives of Tianeptine, which so far have yielded two almost entirely opioid compounds (functioning as mu-opioid receptor and delta-opioid receptor agonists) - As well as a selective kappa-opioid receptor antagonist. (VERY useful in the treatment of depression). - As well as two compounds which function as selective Dopamine / Norepinephrine Reuptake Inhibitors / Dopamine Receptor (D2, D3, D4) Agonists in rodent models. (Not much different in pharmacological action than Amineptine).
As far as sharing personal experiences with Tianeptine, I surprisingly have only ever experimented with dosages as high as 60mg of the sodium salt. I suffer from severe Generalized Anxiety Disorder and Panic Attack Disorder, so the effect that I most notice is an anxiolytic effect, which is quite different than the anxiolytic effect of benzos, since there is no sedation. The anxiolytic effect that I experience from Tianeptine is very short-lived, as others have mentioned.
I also definitely experience an unmistakable opioid effect at 60mg as well, however, the mu-opioid agonization is far too weak for me to call Tianeptine very euphoric, since I am used to very strong full-agonist opiates, and because I dose daily with Buprenorphine which undoubtedly suppresses most of the mu-opioid action of Tianeptine.
I have, however, experimented with doses of up to 200mg of the hydrobromide salt of Proxoleptine (one of the novel and solely opioid compounds that we have produced as a structural relative of Tianeptine), which is much more reminiscent of a fully synthetic opioid like Fentanyl or Pethidine, even when I have previously dosed with Buprenorphine.