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Selective Serotonin Reuptake Enhancer (SSRE) Questions

Kenaz

Bluelighter
Joined
Sep 12, 2007
Messages
643
Location
The Dirty Jerz, Yo...
After writing a book on poppies, I'm working on a book on the history of melancholia. To that end, I've begun researching various antidepressants. I ran into tianeptine when I was doing Power of the Poppy: apparently addicts in Armenia, Russia and the former Soviet Union have taken to shooting up large quantities of crushed Coaxil tablets to get an "opiate-like" high. (For those reading, this is a bad idea. Those who don't believe me should do an image search on "Russia Skeletor girl coaxil" if they're not at work and have a very, very strong stomach). Yet I'm also seeing reports of tianeptine abuse from people seeking a stimulant effect and taking pretty hefty oral doamounts to achieve it. (One guy in Turkey was taking 3 grams a day: the typical dose is 12.5mg TID). So it's obviously not a case of "stimulant in small doses: tickles opiate receptors in big doses," although I suppose it could have different effects if it avoids first pass metabolism and goes straight into the bloodstream.

Theoretically speaking, an SSRE should have the exact opposite therapeutic effect of an SSRI and throw the patient into a pretty nasty depression. Yet most clinical studies suggest that tianeptine is at least as effective as most SSRIs and can sometimes be more useful in patients who don't respond to SSRIs. I've been able to find two theories for its efficacy: one is that it has effect on the glutamatergic system, and the other is that both SSREs and SSRIs ultimately lead to downregulation of the presynaptic autoreceptors. But to my chemically ignorant (if sometimes chemically altered) mind, it kinda sorta sounds like nobody really knows for sure exactly why SSREs do the exact same thing SSRIs do.

Is there anybody here who knows anything about this particular class of compounds and could toss out some ideas on why this chemical appears to act like an opiate, a mild stimulant, and an antidepressant despite what one might expect from its effects?
 
Its a positive allosteric modulator of AMPA receptors, wikipedia can answer your question in depth.
Also, I wouldn't put too much faith in the reports of massive abuse. There are a ton of cases of fake antidepressants being sold that are in reality just really low doses of some random cheap stimulant.

Not ADD, moving to other drugs
 
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Thanks! Very helpful information.

The reports of Coaxil abuse in the Former Soviet Republics are pretty well-documented. And the clinical trials for tianeptine mentioned that some people really liked the short-term stimulation that appears before the antidepressant effects take place. So it appears there is some potential for abuse, although all the reports I saw indicated it was pretty low. I wish I could remember the name of the BLer from Georgia (in the Caucasus mountains, not the southern US) who had shot Coaxil for a while.

Anyway, let me follow up with research based on your leads and see what else I come up with.
 
I always found it funny that SSRE's have proven to be as or more effective than SSRI's, generally speaking. Just goes to show how flawed the current first line of treatment for depression is, and how much we fail to understand about the pharmacodynamics as well as the disorder itself.

Very interesting compound; an SSRE which is structurally similar to a tricyclic, and also has an effect on DA, AMPA and NMDA receptors... Actually sounds like a potentially effective antidepressant.

Glad you're still writing Kenaz- Sorry I don't have more to add:)
 
Well virtually every antidepressant produces the same downstream changes to a large extent, be it by SERT inhibition, NET inhibition, or by (ant)agonizing a handful of receptors there is a distinct pattern seen for virtually all drugs.

AMPA modulation appears to have mixed results on 5HT uptake, but the whole SSRE bit was mainly to explain how this stuff worked to a public that has a 8th grade reading level. You're not going to explain various neurotransmitter systems to someone who can't do basic cell biology.

But, my take on it is its going to be like modafinil. It shows a ton of promise for a lot of conditions but will at best be a second or third line treatment if it ever gets approved for them. But, here's to hoping research on it turns up more info on its relatively unique pharmacology.
 
morphonorconic: glad you enjoy the writing. I find tianeptine interesting because it seems to have a number of possible pharmacological applications, yet is unlikely to get much traction in the US because it's out of patent protection. (There's a chance it may be patented specifically as a medication for IBS, in which case doctors could prescribe it off-label for depression). And the abuse patterns around it are fascinating. Though I'm not sure what to make of Russian addicts using it as a heroin substitute, seeing as how Russians will shoot up damn near anything. This is the country which brought us krokodil and intravenous anticholinergic eyedrops. In Russia, drug makes war on you.

Epsilon Alpha: The AMPA modulation is fascinating. There are other examples of SSREs that have antidepressant AND depressant properties. Reserpine was an early serotonin-depleting drug that caused profound depression in some patients -- yet snakeroot tea (which contains reserpine as its active ingredient) is an antidepressant in Ayurvedic medicine.
 
Epsilon Alpha: The AMPA modulation is fascinating. There are other examples of SSREs that have antidepressant AND depressant properties. Reserpine was an early serotonin-depleting drug that caused profound depression in some patients -- yet snakeroot tea (which contains reserpine as its active ingredient) is an antidepressant in Ayurvedic medicine.

I recall an interesting paper from 2009 titled "the dose makes the poison" if you want to search it up, its very accessible to laypeople and explains why like nicotine and opioids can be both stimulating and sedating. For the life of me I can't remember the author though :/
 
ah i wish ssres were legal in germany. technically my psychiatrist could prescribe them so i get them from austria, i even meet the clinical criteria for it (when six proven medical treatments have failed). currently i'm on mitrazepine and selegiline, but i had to acquire the selegiline through semi-legal sources and my psychiatrist won't prescribe them either because they're only indicated for treatment of parkinson in germany.
sorry for the rant, i really wanted to take tianeptine instead of the venlafaxine i got which does absolutely sweet fuck all.
and people wonder why i mistrust all medical personell.
 
ah i wish ssres were legal in germany. technically my psychiatrist could prescribe them so i get them from austria, i even meet the clinical criteria for it (when six proven medical treatments have failed). currently i'm on mitrazepine and selegiline, but i had to acquire the selegiline through semi-legal sources and my psychiatrist won't prescribe them either because they're only indicated for treatment of parkinson in germany.
sorry for the rant, i really wanted to take tianeptine instead of the venlafaxine i got which does absolutely sweet fuck all.
and people wonder why i mistrust all medical personell.

just happened to stumble upon this post and im glad to tell you, tianeptine is being sold in germany since november 2012 under the name Tianeurax
 
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