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Tianeptine discovered to be MOR agonist

A

Abject

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Dec 14, 2012
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As the title says, it's been discovered tianeptine has activity at MOR (Ki of 383±183 nM, EC50 of 194±70 nM) and at a much lesser extent DOR.
(source)

In the discussion, they say: In humans, a single dose of tianeptine (12.5 mg) results in ~1 μM maximal concentration of the drug in the plasma.
Can someone expand on why they've called that the maximal concentration? Are they saying MOR is "saturated" at 12.5mg?

I happen to have some tianeptine laying around and have taken in doses up to 60mg with no "opioid feelings"
 
Maximal concentration in the plasma means peak plasma concentration, it doesn't mean it's the concentration you need to saturate MOP receptors. The affinity of tianeptine at MOP is very low compared to morphine's affinity which is ~2 nM when [3H]-DAMGO is used as a radioligand and EC50 is much lower for morphine too (source). The conclusion in the article is that mu agonism may be responsible for tianeptine's antidepressant effects, but it doesn't automatically mean that you're going to get a strong opioid buzz from it. In theory you would need a much higher dose of tianeptine than 60mg to get effects comparable even to 10mg of morphine i.v.

Perhaps someone with more knowledge and experience in pharmacodynamics can elaborate more giving you more numbers, but the general conclusion is that tianeptine is way too weak to produce an opioid high at doses prescribed for antidepressant effects.
 
Tianeptine is used recreationally with doses being several times above the therapeutic (reports ranging from 75mg to more than 100mg) - in Russia there were some cases of people injecting crushed pills and getting severe thrombosis and tissue damage from fillers not dissolving correctly.

I've tried it occasionally with 75-100mg - there is something, it feels good but far from strong. Using the regular dose, 3x 12.5mg per day did nothing at all for me. I'm wondering if this stuff really works for some, or if it's mostly placebo ... but on the other side, France even scheduled tianeptine recently..
 
I completely forgot about cases of abuse in Russia. The peak concentration is likely higher after i.v. injection, so perhaps there is some light opioid high. I actually once read an opinion in the past that tianeptine felt like a roll. I was once prescribed it too when I was a teenager and it gave me a slight mood increase after 37.5mg taken at once, but it was almost indistinguishable from placebo, I could compare it to a mood lift after eating more cheese or bananas now. I was already taking codeine then though. It felt neither like an opioid nor like a roll to be honest.
 
Thanks for the input guys

From my understanding the maximal concentration is, as it's name implies and I somehow completely mistook, the peak plasma (~1 μM) reached at a specified dose? (12.5mg)
Although higher dose would result in a greater maximal concentration, I assume it's far from linear and an individual property? Hence the need for maximal concentration?
 
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That's right, the peak concentration (Cmax) is the maximal concentration (in this case in the plasma) after a single dose. It doesn't behave linearly and depends on a lot of factors. Cmax may be different for the same dose of the same drug depending on the route of administration, e.g. the same dose given i.v. shall give a higher Cmax than given p.o., so intravenous users of tianeptine may get a much more pronounced effect than oral users. However, I don't suggest that anyone should take tianeptine intravenously as the possible risk certainly outweighs any positive effects.
 
Thanks for sharing! I've been wondering how active it is at MOR, because it feels too good to not have Some activity there. I love the stuff. Taking high doses3 weeks on 1 week off is great fun and hasn't been problematic.
 
I scored some tianeptine the other day from a popular Lift website, and have tried it twice now. One ~40mg dose didn't produce any discernible effects. This morning I weighed out 100mg, but then decided that was too much and i squeezed a little clump out of the capsule, bringing the dose down to most likely ~60-70mg. About 2 hours after taking the capsule with a coffee and a bagel, I did get a sudden brightening/saturation of colors, perhaps some light stimulation (coffee?) and just a subtle 'change in perception' but definitely nothing even knocking on the door of euphoria or anxiolysis. I don't feel more focused, talkative, positive, or anything desirable really. I did notice a slight 'odor' coming from my skin kind of like what you get from mephedrone or 2C-E, where your sweat smells ever-so-slightly chemically. Not bad though, and it's gone already.

I also tried adrafinil for the first time earlier this morning, ~300mg, that didn't do diddly squat. The tianeptine was ingested at ~1:30pm.

Tomorrow I will try a full 100mg dose. If that does not produce these 'opiate effects', then I'm going to shelf this for a while. I can see this getting scheduled REAL soon though, especially with this very recent information, so stock up if it does work for you.
 
^ This is much like how I reacted to the tianeptine ... so either effects vary greatly from person to person, or they in Russia were taking really huge doses. At least it does not feel directly unsafe to go higher, as there are no clear adverse effects.

I am not yet sure about its qualities as an antidepressant. Usually I do judge the power of a chemical by how it feels, but maybe this one is really different and the point that actually getting a tolerance to it could be the intended way to get antidepressant effects (e.g. the brain adjusting by releasing more serotonin, and/or glutamate modulation).

But I have an unusual high natural tolerance to opiates, requiring more than 100mg of AH-7921 to get a remarkable effect (and this is said to be 75% the potency of morphine) and this is not full strength yet- and even then, opiates don't make me euphoric really. This also led me to think about if I have an endorphin dysfunction causing some of my problems - would make sense as kappa antagonism works for some treatment resistive depressed individuals..
 
I don't have any opioid tolerance and 62,5mg was definitely anxiolytic, similar to low doses of tramadol. It helped me to quit smoking too. The study demonstrates that tianeptine is a pretty selective mu-opioid agonist, so don't worry, it won't fuck with your serotonin system. The "SSRE" and NMDA effects are downstream, not direct.
 
I think I dosed way lower than I originally thought, so today I weighed out ~80mg. Let's see what happens.

I'm not sure what I'll feel though because I do have an opioid tolerance.
 
I've been toying with the idea of trying a rec dose..
I've only got 34 pills left (425mg) but as it doesn't really help with my depression I don't see the point in conserving my supply, and I could always order more (or go through an RC vendor as you seem to have)
 
Eeeee be careful guys, you never know if you're the one with the fucked up physiology and rare terrible reaction. Work your way up if you must.

Interesting I just found this archived thread today: Tianeptine - Inexpereinced - Opiate Buzz

In case there was any doubt that Bluelighters often know more than the most up to date medical literature.
 
I saw that thread, some good info there.

I'm definitely trying to be careful, haven't had any reactions that I'm concerned about. I've also read more threads of people megadosing and not only achieving the opioid buzz, but also not getting any negative side effects. Having said that, this is quite out of my character to be playing with RC's like this, especially looking for a buzz. I'm in this game for nootropics and stumbled across this obvious distraction.

I will probably shelf it for the better part of a week before experimenting again. My ~80mg dose today again produce the effects I described yesterday, however, this time I potentially felt some anxiolysis, dare I say a slight buzz with perhaps some added pleasant stimulation. Definitely not euphoria yet, but it shows more promise in this area than any other nootropic that's for sure.
 
Abstained for a day, and now I am about to dose 110mg. I won't be going any higher than this. My previous high-ish doses have yet to produce any negative effects, actually quite pleasant. I'm noticing very smooth stimulation, anxiolysis, colors/lights brightening and becoming more saturated (kinda mushroom-like), and contrary to what folks have been saying about short half-life, I feel like it lasts the whole rest of the day. I can't say if it's affecting sleep at all because I always sleep terribly, however for what it's worth, these past two nights of sleep have been much better than usual. So far, I'm a big fan of this one, definitely is fun but to be honest I don't see a whole lot of nootropic value. Nothing like aniracetam which I feel gives me a second brain to use simultaneously.

I take kratom daily which is kinda hit or miss when it comes to constricting my pupils significantly, but when tianeptine has been taken, I can look straight up loaded.
 
Seattle_Stranger said:
to be honest I don't see a whole lot of nootropic value.
Click to expand...

Seeing as Tianeptine indirectly affects AMPA and NMDA glutamate recoptors, releases BNDF and increases neuroplasticity I don't really see how you can make that comment.
Of course, building up a tolerance with taking 900% of a therapeutic dose would affect it's nootropic effects.

That being said, I'm all out of Tianeptine. I took 175mg which was too much, I got some itching and hot flushes and it made me nauseous to the point of puking (after having some tobacco) followed by 125mg on it's own and 125mg with ~60mg DXM.
I don't think I enjoy opioids (i've only tried PST, codeine and a very small dose of oxy) but contrary to your experience I've found Tianeptine to be sedating (i was almost "nodding") in higher doses as opposed to stimulating.
 
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Abject said:
Seeing as Tianeptine indirectly affects AMPA and NMDA glutamate recoptors, releases BNDF and increases neuroplasticity I don't really see how you can make that comment.
Of course, building up a tolerance with taking 900% of a therapeutic dose would affect it's nootropic effects.

That being said, I'm all out of Tianeptine. I took 175mg which was too much, I got some itching and hot flushes and it made me nauseous to the point of puking (after having some tobacco) followed by 125mg on it's own and 125mg with ~60mg DXM.
I don't think I enjoy opioids (i've only tried PST, codeine and a very small dose of oxy) but contrary to your experience I've found Tianeptine to be sedating (i was almost "nodding") in higher doses as opposed to stimulating.
Click to expand...

The very next sentence should have explained it. I take aniracetam, noopept, phenylpiracetam and various other nootropics in various combinations almost every day, and I have not experienced any comparable subjective effects with tianeptine such as the profound boost in thinking/memory abilities. I'm on about ~2g phenibut right now, taken way earlier this morning, and it feels eerily similar to tianeptine which is ironic because some people call phenibut a "nootropic" as well, which I also disagree with. Maybe if I HAD to get some work done, and I was feeling distracted and anxious about something, then OK maybe yeah...but in that case kratom would be my go-to, not tianeptine.

My comment had absolutely nothing to do with the pharmacokinetics, I'm talking about subjective experience.
 
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So the new research past couple years claims pure MOR Agonists are not that abusable apparently kappa is required and delta to some extent. Opioid receptors don't just dimerize they form a dimer of dimers of various opiate Receptor domains(oligmerization)..

Apparently Tiantepine is a dor/mor agonist though.

My feeling is Tiantepine can't cross the brain that well(sodium salt of carboxylic acid not amino acid like but still very nonpolar molecule ) it still does but higher doses are needed with tolerance which also infers primary metabolism first though. It does look like a substrate for FAAH like acetaminophen in the brain I'd guess.

Better Tiantepine? Acetylate the carboxylic acid, I'm guessing they had to keep the salt to improve solubility. The acyl ester should be nice. Also if the amine is methylated again it may be even more opiate like.

Zedsdead
 
Very interesting, I am sure this find will cause a few ripples, great last post as well Zed but part of me really hates suggestions of RC antideprassant/opiate hybrids, sure there is a market but lets just not go there.

But while we are at it why not just pyrrole the amine and throw a ketone on? This is all said as a joke I don't want anyone thinking this post is serious.

PV/cathinone/AD/opiate RC - sure sounds like the worst thing in the world.

To get this back on track, what was it that was said about France in this thread? Anyone from France able to speak about tianeptine?
 
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