I am aware of tianeptine (which can't be prescribed in the UK) but there are 2 better known antidepressants that are safe for RLS. Wellbutrin which may also help RLS (also can't be prescribed in the UK except for smoking cessation) and trazodone which also helps anxiety and insomnia.
correct sue, like always. but the antidepressant effect is not relevant in my context.
if there were not the short half-life, i am relatively sure that this would be a much safer alternative to conventional WED drugs (primarily conventional opioids): theoretically.
what really interests me is the (possibly atypical) μ-opioid receptor agonist property of tianeptine, and of course all the rest, like NMDA antagonism on the glycine-b site, et cetera). unfortunately it's not available in many countries, as you already pointed out. but at least in my country it is available (and cheap).
the point was: this is a promising, relatively "old" drug, and there is no research at all in the context of WED(/RLS) + tianeptine, despite its interesting properties, which makes me angry. again.
Hi Snoemata, I disagree with you. I can’t imagine this drug ever helping the symptoms of RLS, and to the contrary, I would guess that it would make the symptoms worse, if taken at night. This is one of several articles, including your first one, that reveals Tianeptine up-regulates D2/D3 receptors. researchgate.net/publicatio...
This is exactly what we need. We need to up-regulate our dopamine receptors by taking benign, short-acting substances during the day or undertaking activities like anaerobic exercise or severe calorie restriction. No pain, no gain. The articles all indicate that this drug has no “affinity”for our dopamine receptors - meaning no agonism or antagonism. That doesn’t matter because somehow, someway, it clearly has the potential to up-regulate our receptors.
Here’s the relevant paragraph from your first article:
“Tianeptine modestly enhances the mesolimbic release of dopamine and potentiates CNS D2 and D3 receptors. Tianeptine has no affinity for the dopamine transporter or the dopamine receptors.”
Forget the medical and scientific community. The cavalry isn’t coming. You and I and everyone on here are the cavalry. If we don’t come up with solutions and try them on ourselves, no one will. Don’t get angry, get to experimenting on yourself. That’s what I do, always, and for all conditions, for better or worse. Feeling lucky?
But you pointed out the MOR (mu opiod receiptor) agonist are drivers of neuroinflammation. If that is the basis of Tianeptine's benefit, then is it an advantage over simple opioids? I guess in the '90's Prozac just won the competition for depression and the market went with SSRI's? The opiod stimulation, potential for abuse and withdrawal from high doses seem to given it unfavourable drug scheduling that may have limited its popularity with prescribers.
I only have a couple of hours a day to read these articles so it is hard to catch up on 30+ yrs of research. That was a long review article. The writer reveals he has worked for the company that makes Tianeptine - bias or why he writes with so much knowledge, who knows?
There was an announcement of a new once daily version going into phase 2 trials in '21 by Tonix. This was at the end of the press release -
Tonix has added naloxone to the TNX-601 CR tablet as a deterrent to parenteral abuse, because tianeptine is a weak mu-opioid receptor agonist and has been linked to illicit misuse at much higher doses than those reported to be effective in the treatment of MDD
0: no, i pointed out that the kappa-opioid receptor antagonism of buprenorphine is related to neuroinflammation (microglia), adding complexity to the already complex neurotoxic effects of opioids. but i do not want to go back to this post again.
tianeptine is possibly a biased agonist at the μ-opioid receptor. this is a positive thing and should be studied in more detail. but that doesn't happen in the scientific community. reason: not profitable. neither for elsevier (anymore), nor for other pharmaceutical companies (for obvious reasons). note: your link is a bit of a relativization of that statement. maybe 4 bits.
i don't care about these stories about stupid people abusing this substance because i have a serious neurodegenerative disease called WED at a very young age. the same statement applies to pregabalin/gabapentin/opioids. end of (that) story.
is highly interesting. thank you very much (+ adding naloxone in the right ratio is "a good idea" - mainly for marketing reasons and wider acceptance by the ever-worried abuse!-crowd).
2: i am not a fan of using methadone against WED. the only interesting effect (for me) is its nmda-antagonism, and that can be achieved with (for example) a less toxic (+ in some sense "atypical") opioid like tilidine (again, not available in most countries). so, i have no strong opinion about methadone in the context of this forum.
in general: i don't care that the second link is from elsevier, because there are a lot of independent studies that confirm its interesting properties. the reason why tianeptine was not accepted as an effective antidepressant in most countries was because it was expensive and showed no additional advantages compared to the millions of other "antidepressants" available. money.
as i pointed out in my reply to sue, the antidepressant properties are not relevant in this context anyway.
there are far more aspects to this drug that are even more interesting than its possibly distinct action at μ-opioid receptors ((or the dopaminergic system - like bupropion - in the context of the nucleus accumbens) via adenosine a1 receptor modulation)) - in the context of WED/RLS. in fact, these features are not that important to me.
again: these are only theoretical possibly positive effects in the context of this forum. i have no idea if tianeptine resp. TNX-601 CR (again, thx) has any positive effect regarding WED.
i am not saying: "possible wonder drug", "possible miracle drug", "possibly free of serious side effects" and so on + i am never really satisfied if the symptoms are relieved with drug xyz, because i consider any current "medication" against WED to be toxic (in a broad spectrum).
sum. and reaction to other users, past or future. the actual point of my post was already pointed out in another response. research. doing something. but the "WED-pipeline" is still a joke. science is in deep trouble. for decades. even in physics (that, i know for sure).
learner, i hope that you will never give up on learning and adapting, even though it may seem like a sisyphean task.
albert camus philosophized: "imagine sisyphus happy". well, i am simply angry.
You seem like a smart woman. Ever wonder why RLS is mostly a condition of the night? I think because our serum iron (not ferritin) plummets at night, with a nadir of midnight. How about you try 50mg of ferrous bisglycinate on an empty stomach about an hour before bed. It dissolves my RLS in one hour for one night. Give it a shot, whaddya got to lose 😁 Then it could free you up to explore ways for us to up-regulate our lousy dopamine receptors which ultimately is probably the best treatment.
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Iron, Opioids and great information
RLS/ WED along with ED
RLS SUPPLEMENT UPDATE
Still having success (no RLS for almost a month now) with B1 supplement and celery juicing.
My take on rls and copper
