Tianeptine sodium milligram morphine equivalants (MME) estimate?

[Essessarai]

Thus far I have been unable to get a good estimate of tianeptine’s analgesic activity relative to other opioids. For practical clinical purposes this is often reckoned as milligram morphine equivalents, that is the dosage of oral morphine which would provide pain relief equivalent to a milligram of the opioid in question. This can aid in determining risk of overdose, converting between methods of administration and in rotating opioids.

I acknowledge that as a concept, MME is not without issues, and would stress that those tasks which MME can aid are not purely quantitative and should be approached holistically, acknowledging that numerous factors affect the subjective experience of analgesia, and risk of toxicity. The FDA made materials available from a conference they held on the subject of MME ( https://www.fda.gov/drugs/news-even...and-knowledge-gaps-research-opportunities-and ), and I acknowledge that there are important caveats to the concept. Furthermore, it’s reasonable to assume that euphoria is not always proportional to analgesia. Nevertheless MME cab be useful. Has anyone estimated tianeptine’s MME?

I have heard that the minimum MOR-agonist dose is about 150mg. I would expect this corresponds to perhaps 5-10mg of morphine sulfate (oral). Below that you don’t get any opioid like effects. Thus Tianeptine is not high potency and the oral-oral MME is on the order of 0.03 - 0.06mg.

From a harm reduction standpoint, it would be useful to know about how much of a substitute d opioid would achieve a similar effect as a maintenance or recreational dose of Tianeptine, potentially reducing overdose risk. So far I haven’t found any pharm literature on this topic, so reaching out to the forum in case this is indeed known.

 

[izo]

I would expect this corresponds to perhaps 5-10mg of morphine sulfate (oral)

id say 150mg are more like 15mg of morphine, never weighted it. 140mg are like around 50mg of codein if that helps.

 

[AlsoTapered]

Tianeptine appears to be a SUPERAGONIST. Don't mistake that term to mean 'highly potent', a superagonist is a drug that produces agonist effects that are greater than the bodies own ligands at an appropriate concentation.

Specifically tianeptine is a low affinity superagonist so below a requires quite a lot before any activity is noted (a concentration an order of magnitude higher than endorphins) BUT it also appears, like previously discovered superagonists, that it produces tolerance and dependence that is out of proportion with it's potency.

I say 'appears to be' because although not stated as such, the papers I have linked to (which provides IC50 values) DOES term it 'low affinity' and 'high efficacy' - the latter (with appropriate data) showing it's efficacy to be higher than DAMGO and a range of other peptide ligands.

 

[Essessarai]

My own experience is that it does not behave like typical opioid with respect to opioid effects (setting aside the other target actions, like NE, NMDAr or whatever the targets are…). Ceiling effects, unpredictable subjective effect, even mild muscle dystonias at high dosas (may be electrolyte driven rather than central/basal ganglia dopamine blockade driven).

I hear your superagonist argument and I’m not sure what post the articles are in, but seems reasonable that an assay with Tianeptine producing more response than DAMGO would support a superagonist designation. And from a logical perspective, you might expect a superagonist to produce more prolonged and intense withdrawal, as the gap between endogenous agonism and superagonist effect would be wider. One would expect however that a hyperbolic taper would be able to manage this.

This actually explains some of my own experience in the last week. I spent a ton of money on a beautiful resort vacation out of US, and used it as motivation to taper from my massive Tia habit (~12-15g/day). Tapered from that over 10 weeks, but had a setback when my dog pulled me down a slope on a hike and I broke a rib, so made it to about 3.5g/day by my departure. Considering the relative ease of the taper thus far, and significantly reduced dose magnitude, I brought only enough with me for a taper of approx 20% per day. By day 5 I was unable to sleep, RLS, cold sweats, so had to cop in town. Where there’s a will there’s a way. Got dubiously sourced oxycodone 30 mg for last 2.5 days. Assuming they were as advertised, those are about 45 MME each. Although I did more, I think about 7 of them would have set me straight, and given the failure of my taper, I’d say I needed about 2.5g per day of Tianeptine (70:30 sulfate:sodium). The true strength/content of the pills I copped induces some doubt, and I don’t weigh the tia (use packed capsules for consistency) but assuming as stated, my daily requirement was approx 325 MME and I was straight on 210mg/day OC or 2500mg Tianeptine, then puts Tia 1mg ≈ 0.13 morphine or 150mg Tia ≈ 19.5mg morphine. Given the unknowns I’d say at best this is a sanity check, but I’d with 30% of izo’s estimate, so sounds ok.

Prior to trip I checked with an addictions specialist friend of mine who said he believed that with most subs, fraction of taper is more important than magnitude of taper, however below a certain threshold, you can just stop. All this is to say that if it is indeed a superagonist, that threshold at which you can cut the dose by 100% is probably very low and a long “hyperbolic” taper is probably the only way to go. It also explains why it was so tough to power thru the last 2-3g of taper, which would not have been advised if it’d had a better MME estimate and noted the superagonist effects.

One more small thing. I went 48h with no Tia at all when I was covering with OC. I had no readily identifiable withdrawal related to the aforementioned other target receptors. Obviously an n of one and subjective, but it seems like MOR activity was the only domain of withdrawal, not NE or others (although I have no idea what to expect from NMDA/AMPA modulator w/d).

 

[AlsoTapered]

Opioid-Like Adverse Effects of Tianeptine in Male Rats and Mice

Tianeptine is a mu-opioid receptor (MOR) agonist with increasing reports of abuse in human populations. Preclinical data regarding the abuse potential and other opioid-like adverse effects of tianeptine at supratherapeutic doses are sparse.The present ...

www.ncbi.nlm.nih.gov

'...tianeptine acts as a low-affinity but high-efficacy mu opioid receptor (MOR) agonist...'

And the reference shows it activity being greater than endoligands. Superagonists CAN be potent and indeed the unique structure of tianeptine has made me lose a lot of sleep - about a decade of research now needs revising.

People have studied the QSAR and their are patents and papers on the subject but it even breaks the RO5 so I conclude that we don't truly understand it's activity to even a basic level.

 

[beebs76]

Do you feel like there is any risk of overdose with Tianeptine Sodium? The same type of respiratory depression as other opiates?

 

[AlsoTapered]

Do you feel like there is any risk of overdose with Tianeptine Sodium? The same type of respiratory depression as other opiates?

Fatal intoxication with tianeptine (Stablon) - PubMed

Tianeptine (Stablon), although structurally similar to tricyclic antidepressants, acts by enhancing the reuptake of serotonin. A fatal case is presented involving a 26-year-old man, found lying in bed with a "mushroom of foam" around his mouth. Empty blister packs of Stablon and a suicide note...

pubmed.ncbi.nlm.nih.gov

Acute Toxicity From Intravenous Use of the Tricyclic Antidepressant Tianeptine

Tianeptine (7-[([3-chloro-6,11]-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl) amino] heptanoic acid S, S dioxide) is a tricyclic compound prescribed as an antidepressant in European countries, but is not currently approved for use in the United States. ...

www.ncbi.nlm.nih.gov

https://journals.sagepub.com/doi/pdf/10.1177/0960327110372403

Yes. Most fatalities appear to involve polydrug abuse but I think it's very likely that the majority of overdoses occurred in Russia because IV usage is so much more prevalent.

It's an opioid. Not a particularly potent one but in overdose it appears to cause respiratory collapse in the same way other opioids do.

As stated, it's demonstrates low-affinity but high efficacy so I think it poses a special risk because the dose-response curve is likely to be quite unforgiving (at the doses taken to produce opioid effects).

I have to say that research does suggest that it's a really nasty drug. People report that tolerance and dependence occur quickly and the withdrawal syndrome seems out of all proportion to it's actually potency as an opioid.

Be careful.

 

[beebs76]

The harsh part of the withdrawal is probably the the SSRI/ SNRI impact of the medication IMO.

 

[AlsoTapered]

The harsh part of the withdrawal is probably the the SSRI/ SNRI impact of the medication IMO.

The people who experimented for an extended period are all quite experienced having similarly experimented with both tramadol and tapentadol. So obviously the first question was if monoamine activity had an impart on the withdrawal syndrome.

They were all adamant that a sufficient dose of a more traditional opioid reversed the withdrawal syndrome.

Of course, it's purely subjective - we have no data either way but I did think to ask and they in turn had asked themselves the same question.

BTW have you noted that medically raecemic tianeptine is used. Now, far be it for me to be suspicious of the pharmaceutical industry but it's been established that (R) tianeptine is about x10 more potent than (S) tianeptine. That happens to reflect the activity of ciramadol.

You may ask why they would make the raecemate given that, with an optimized sysnthesis, (R) tianeptine would be a cheaper target (since the dosage could be halved). But if it hasn't happened already, I would be prepared to bet that their are plans to 'discover' that (R) tianeptine is a better antidepressant... and get another 20 years of patent protection.

The above trick has been used numerous times. Citalopram led to Escitalopram, Zopiclone begat Eszopiclone, Ketamine has been replaced by Esketamine and so forth. It takes a special kind of person to work in drug development knowing that a better product is being held back to ensure maximum profit...

Sorry to OT but it gets to me.

 

[beebs76]

The (R) Tianeptine being the Sodium and the (S) being Sulfate, correct? Are you, in part, saying that Sodium Tianeptine is much more overdose an overdose risk than Sulfate? I would tend to agree with that. I think the fast acting version is much more serious at high doses. But you also think the Sodium is better for depression that the longer acting Sulfate?

BTW, I have taken Taeneptol. I failed a drug test on it. The drug test said I was on codeine, Opium and PCP. Let's just say I didn't get the job and when the HR Lady called me back she was like, "What sort of stuff are you on? Are you trying to kill yourself?" I told here I was taking a drug called Tapentadol for pain, which I got from India (Signature brand) and that the ingredients in it must be that of what I tested for, or that it was a false positive for those things.

Do you think Tap is a bad drug? It did a lot for my treatment resistant depression but getting it was not sustainable and I ran out. Now that drug price has gone through the roof.

 

[beebs76]

The people who experimented for an extended period are all quite experienced having similarly experimented with both tramadol and tapentadol. So obviously the first question was if monoamine activity had an impart on the withdrawal syndrome.

They were all adamant that a sufficient dose of a more traditional opioid reversed the withdrawal syndrome.

Of course, it's purely subjective - we have no data either way but I did think to ask and they in turn had asked themselves the same question.

BTW have you noted that medically raecemic tianeptine is used. Now, far be it for me to be suspicious of the pharmaceutical industry but it's been established that (R) tianeptine is about x10 more potent than (S) tianeptine. That happens to reflect the activity of ciramadol.

You may ask why they would make the raecemate given that, with an optimized sysnthesis, (R) tianeptine would be a cheaper target (since the dosage could be halved). But if it hasn't happened already, I would be prepared to bet that their are plans to 'discover' that (R) tianeptine is a better antidepressant... and get another 20 years of patent protection.

The above trick has been used numerous times. Citalopram led to Escitalopram, Zopiclone begat Eszopiclone, Ketamine has been replaced by Esketamine and so forth. It takes a special kind of person to work in drug development knowing that a better product is being held back to ensure maximum profit...

Sorry to OT but it gets to me.

150MG of Tia Suflate feels about like 100MG of Tap Sustained Release to me. The Tap SR seems to last longer - Maybe 4 hours longer in duration - than the Tia Sulfate IMO. I'd say Tia Sulfate's "Happy Feeling) lasts about 4-6 hours and Tap SR lases about 8-10 hours. Obviously, this is all anecdotal. Just what I "feel."

I did run into a problem with Tap SR. I noticed the sudden occurrence of Pelvic Floor Disorder that would come and go over time. I tooked Tap for 6 months daily, and when I stopped, the Pelvic Pain went away in about 2 weeks. I don't get that same pelvic floor pain with Tia Sulfate.

 

[Essessarai]

do you have a citation for the R enantiomer being the 10 x more potent? Had not heard of this. Sure, enantiomer isolation is a tried and true strategy for patent extension. However no version of Tianeptine is FDA approved, and if there were a US patent it expired long ago. Perhaps if Pharma did apply for approval it might be for (R-)Tianeptine. That said, I have much in the way of knowledge of FDA procedures, but part of the story of escitalopram is that the S enantiomer has a somewhat different (and I would argue more tolerable) side effect profile. If it is the case that some of the more vexing adverse effects of Tianeptine are attributable to S enantiomer, then R might be an attractive drug. Also, if it is 10x more potent, the. One might expect that the isolated R enantiomer would be about 5x more potent than the racemic mixture and thus potentially more tolerable by IN and IV routes.

 

[AlsoTapered]

Elsewhere I have posted patents which detail the activity of the two enantiomers. Researchers were able to optimize the MOR activity with one example apparently being over 600 times more potent.

I started a thread on it.