Retigabine (Trobalt, Potiga) — General Discussion

[nills]

Is there any correlation between the good results and les time of having Tinnitus ... I saw some good results with people that only had T for about a year. Anyone with chronic T for many years have good results?

Sorry guys if this has been answered all ready but the thread has become so vast I didn`t want to start looking ...

 

[1MW]

I made a comparison RTG vs NAC in acute relief of T.
Today at night i had bad worsening so i took 300mg RTG after 1 hour T improved (not very much)
after 4 hours the improvement lost and i returned to baseline then i got about 300mg NAC
and after 1 hour the improvement was 2 times more than RTG.
To me both RTG and NAC make temporary improvement but i think NAC is more effective.

 

[TomKA]

@Albertus
Maybe that's why the patent for this drug, filed 15 years ago, was noted in being useful in the treatment of tinnitus.

0020 KCNQ2/3 potassium channel openers including retigabine are further useful in the treatment of tinnitus

http://www.google.com/patents/EP1407768A2?cl=en

Unfortunately the only THOUGHT that it MAY be a treatment for T - if you read the complete text it maybe help for nearly everything (even HIV - WHY????)...

"However, there is no teaching as to whether KCNQ2/3 openers or dosers would be of use in the above diseases and no in vitro or in vivo support for these suggestions."

 

[Christian78]

Unfortunately the only THOUGHT that it MAY be a treatment for T - if you read the complete text it maybe help for nearly everything (even HIV - WHY????)...

"However, there is no teaching as to whether KCNQ2/3 openers or dosers would be of use in the above diseases and no in vitro or in vivo support for these suggestions."

Does anyone know how long time trobalt needs to be taken so that he reaches effect?

I stopped it for some days to check all this pain sensitivity does it come from it, but pain did not go away so i restarted. I cant find how much time does it needs to be taken before it has effect (not tinnitus effect but usual effect)

 

[undecided]

Is there any correlation between the good results and les time of having Tinnitus ... I saw some good results with people that only had T for about a year. Anyone with chronic T for many years have good results?

Sorry guys if this has been answered all ready but the thread has become so vast I didn`t want to start looking ...

I believe that @RaZaH has been having some good results and he has had T for more than a year.

 

[SteveO]

Kv7 modulators are far from kv3.1.

Fyi one kv3.1 modulator is SKA 31 which u can get online. Isnt that AUT00063 ? So targeting that area

Fyi
http://www.aurorabiomed.com/download/presentations/pres09/Heike_Wulff.pdf

One online retail for bulk sciencetesting etc
http://www.sigmaaldrich.com/catalog/product/sigma/s5576?lang=en®ion=GB

Shared via the Google app


Sent from my iPad

 

[Juan Carlos]

Kv7 modulators are far from kv3.1.

Fyi one kv3.1 modulator is SKA 31 which u can get online. Isnt that AUT00063 ? So targeting that area

Fyi
http://www.aurorabiomed.com/download/presentations/pres09/Heike_Wulff.pdf

One online retail for bulk sciencetesting etc
http://www.sigmaaldrich.com/catalog/product/sigma/s5576?lang=en®ion=GB

Shared via the Google app


Sent from my iPad

Pity its too expensive to be viable, but maybe take the formula and order to the chinese people for a reasonable price?

 

[SoulStation]

Fyi one kv3.1 modulator is SKA 31

Sounds like the name of a band I liked going through my big ska phase. Lol.

 

[1MW]

Have anyone edema in his legs from RTG (sign of renal failure) ?

 

[tomm]

I had a BUN test done before ret and about 2-3 weeks in. My values didn't change.

 

[Juan Carlos]

I had a BUN test done before ret and about 2-3 weeks in. My values didn't change.

Also all my test were fine. also checked my eyes, all fine.

BTW, as read in post of Autifony, it seems to be confirmed what I always believed: the more time u been on T, the more time u need to get cured, but i guess there is no limit time be able to get cure suposing AUT works

 

[Mo_Mo]

Have anyone edema in his legs from RTG (sign of renal failure) ?

Isn't that a side effect of corticosteroids also I would guess with RTG side effect of urination retention it would make it worse
Hence I don't think it is a clever idea to take corticosteroids while you take rtg

 

[preslys]

SYNTHESIS OF RETIGABINE ANALOGUES FOR THE TREATMENT OF TINNITUS AND PROGRESS TOWARDS A CONCISE ROUTE TO XJB-5-131

http://d-scholarship.pitt.edu/23723/

 

[Christian78]

did anyone had problem with pains in legs and hands because of trobalt. I cant sit, write, sleep because my legs get numb and so on. Anyone has advice?

 

[amandine]

@preslys

Thanks for posting the paper above.
Please tell me who among us reads all that and understands it?

 

[Zimichael]

@preslys

Thanks for posting the paper above.
Please tell me who among us reads all that and understands it?

For the die-hards, it appears to have some snippets of very "interesting" comments about how Retigabine works (in almost extreme detail) but most of it is stratospheric chemistry, so I glaze over. Someone needs to read it to pull out the "interesting stuff" and do a little summary in plain English.

Volunteers???!!!

Best, Zimichael

 

[amandine]

For the die-hards, it appears to have some snippets of very "interesting" comments about how Retigabine works (in almost extreme detail) but most of it is stratospheric chemistry, so I glaze over. Someone needs to read it to pull out the "interesting stuff" and do a little summary in plain English.

Volunteers???!!!

Best, Zimichael

Thank you Zimichael - now I know that I am not alone in finding reading such texts like walking through a swamp.
By the way, are these smiley face icons on this site? where do you find them?

 

[Mo_Mo]

@Christian78 are you back on trobalt?

 

[Danny Boy]

did anyone had problem with pains in legs and hands because of trobalt. I cant sit, write, sleep because my legs get numb and so on. Anyone has advice?

I had a crazy sensation in my legs, it was like I couldn't sit down and then I had a odd twitch in my face. Crazy. My tinnitus is low now. I'm using chlorella and spirulina, to purify my blood to reduce side-effects, although, I'm unsure if it then reduces the potency of trobalt? Anyone reckon it will?

 

[Danny Boy]

SYNTHESIS OF RETIGABINE ANALOGUES FOR THE TREATMENT OF TINNITUS AND PROGRESS TOWARDS A CONCISE ROUTE TO XJB-5-131

http://d-scholarship.pitt.edu/23723/

I've read this and from what I can tell, trobalt may be more effective vs Autifony's drug? Although, is it? I'm rather confused? If KV7 helps reduce tinnitus and KV3.1 is then the true target, then why are so many people trialling Autifony's drug not having an effect? I mean that KV7+KV3 may be the right combo? I'm sooooo confused right now. Any thoughts, anyone?

 

[maptnh]

I've been a passive reader on this forum for some time now. After reading about some good experiences on this forum, i decided to go to my doctor to ask for Trobalt. To my surprise he was willing to try, and prescripted me 100mg trobalt to start with. Zero pharmacies had these in stock so could not start until today.
How long time (if any) should i expect before hearing any improvements, Taking 100mg x3/day.
And for how long should i take the 100mg before changing to 200mg if needed?

 

[Danny Boy]

I've been a passive reader on this forum for some time now. After reading about some good experiences on this forum, i decided to go to my doctor to ask for Trobalt. To my surprise he was willing to try, and prescripted me 100mg trobalt to start with. Zero pharmacies had these in stock so could not start until today.
How long time (if any) should i expect before hearing any improvements, Taking 100mg x3/day.
And for how long should i take the 100mg before changing to 200mg if needed?

Glad to hear you got some! My doctor won't give me anything unless a specialist agrees.

 

[Danny Boy]

Metal Gear Solid 5 better come out soon, before I run out of trobalt...Because I don't know how long I'd last with my full blown tinnitus. At this volume I'd be ok.

 

[maptnh]

My old doctor gave me nothing either, So i switched
Also had a bad T-period lately. It usually starts getting better after a year or two. My first year with it was really annoying, But sort of get used to it after a while.

 

[RichL]

then why are so many people trialling Autifony's drug not having an effect?

Sorry if someone has replied to this @dboy , What do you mean so many people? I have only read of two on this forum that are trialing with Autifony and the chances that they both have placebo is extremely high!

Please be more careful with misinformed opinions that are very misleading and untrue!

 

[locoyeti]

SYNTHESIS OF RETIGABINE ANALOGUES FOR THE TREATMENT OF TINNITUS AND PROGRESS TOWARDS A CONCISE ROUTE TO XJB-5-131

http://d-scholarship.pitt.edu/23723/

cool paper. my thoughts:
i think basically this guy is a chemist that is creating retigabine analogues that may have better or worse pharmacodynamics / kinetics. the changes to Zone 1 can aid with experimentation that 'would allow us to probe the structure-activity relationship of retigabine' by replacing the Flourine (F) with other groups that can lead to 'improved peptide mimicry, potency, and selectivity'. This is also an interesting quote: 'Decreasing the basicity of the secondary aniline could decrease clearance of the compound.', meaning it could be made more potent. Zone 2 changes are to the carbamate. one sentence stood out: 'The covalently modified compounds showed increased solubility and membrane permeability. '.

i didn't read the mitochondria part of the report, i think that is not really relevant (though may marginally be). basically he is saying, 'hey, i can do all these modifications to this retigabine molecule, and it could be useful in the current tinnitus research using this drug, as well as this other mitochondria research that uses this drug'. It is important in that he is providing researchers more molecules to experiment with.
It remains to be seen if a drug can be made to specifically target the auditory cortex (I am skeptical). the changes made to this drug are basically making it more/less potent via selectivity of Kv7.2/3 channels, clearance rate, increased permeability, etc.
but since Kv7.2/3 are still widely distributed throughout the brain, i don't see how this would reduce the side effects of the drug (if it is more potent to the auditory cortex, it will be equally potent to the other areas of the brain we don't particularly want it to go). let's see how tinnitus research with these compounds will shake out. if it is the case that the compounds won't be selective to the auditory cortex, maybe increasing some other aspects of their effects will yield better results for tinnitus. i'd say overall this is great news on the research front for tinnitus. anyone else have thoughts on this?

 

[dboy]

Sorry if someone has replied to this @dboy , What do you mean so many people? I have only read of two on this forum that are trialing with Autifony and the chances that they both have placebo is extremely high!

Please be more careful with misinformed opinions that are very misleading and untrue!

Hey @Rich L I think you are mixing me up with @Danny Boy.

 

[Zimichael]

cool paper. my thoughts:
i think basically this guy is a chemist that is creating retigabine analogues that may have better or worse pharmacodynamics / kinetics. the changes to Zone 1 can aid with experimentation that 'would allow us to probe the structure-activity relationship of retigabine' by replacing the Flourine (F) with other groups that can lead to 'improved peptide mimicry, potency, and selectivity'. This is also an interesting quote: 'Decreasing the basicity of the secondary aniline could decrease clearance of the compound.', meaning it could be made more potent. Zone 2 changes are to the carbamate. one sentence stood out: 'The covalently modified compounds showed increased solubility and membrane permeability. '.

View attachment 5119


i didn't read the mitochondria part of the report, i think that is not really relevant (though may marginally be). basically he is saying, 'hey, i can do all these modifications to this retigabine molecule, and it could be useful in the current tinnitus research using this drug, as well as this other mitochondria research that uses this drug'. It is important in that he is providing researchers more molecules to experiment with.
It remains to be seen if a drug can be made to specifically target the auditory cortex (I am skeptical). the changes made to this drug are basically making it more/less potent via selectivity of Kv7.2/3 channels, clearance rate, increased permeability, etc.
but since Kv7.2/3 are still widely distributed throughout the brain, i don't see how this would reduce the side effects of the drug (if it is more potent to the auditory cortex, it will be equally potent to the other areas of the brain we don't particularly want it to go). let's see how tinnitus research with these compounds will shake out. if it is the case that the compounds won't be selective to the auditory cortex, maybe increasing some other aspects of their effects will yield better results for tinnitus. i'd say overall this is great news on the research front for tinnitus. anyone else have thoughts on this?

Hey thanks much Loco...I figured you might get through it. (Are you serious @Danny Boy that you 'get' all this high chemistry stuff in there??? Maybe you majored in bio-chem for all I know).
Anyway, my skimpy perusal showed that if anyone wants a down and dirty close up look at the "molecular" (for want of a better word) activity and MOA etc. this paper would probably provide it.

I noted some "interesting" comments in places where I still found that I understood the English language...like:

Alteration of the fluorophenyl and carbamate functionalities present in the parent compound resulted in the synthesis of a small library of compounds with the goal of improving potency and selectivity for the Kv7.2/3 potassium ion channels. In vivo and in vitro testing is underway to determine efficacy.
...Team Trobalt may be able to update more on this soon.

A particularly difficult aspect of treating tinnitus was its ambiguous molecular origin. Tinnitus appears to have a staggering numbers of factors associated with its induction and continuation. Objective tinnitus tends to result from vascular abnormalities5 or spontaneous otoacoustic emissions6 while cochlear lesions (damage or reduced function of the cochlea) are the most obvious physical cause of subjective tinnitus. Those with tinnitus typically have cochlear dead regions7 or outer hair cell damage. 8 These observations only explain the induction of tinnitus, however, and not its persistence after the initial injury.
Then a bit later: With a stunning lack of options for those affected by tinnitus, examination of compounds that modulate Kv7 ion channel activity could lead to the development of an effective treatment.
...Yep we know this!!!

In particular, reduced Kv7 ion channel activity prevents the termination of action potentials, leading to simulated auditory input (i.e. tinnitus)....and then a bit later: Voltage-gated potassium ion channels (Kv ion channels) have 12 subfamilies distinguished by their amino acid sequence (abbreviated with KvX.Y nomenclature, where X is the family and Y, the specific family member) and almost exclusively terminate action potentials in neurons.
...Ummmm, back to my crude thesis: KICK THE DOORS OPEN!

Opening and closing of the pore domain is controlled by a glycinegating hinge that was identified through analysis of crystal structures of open and closed bacterial potassium ion channels. 26 The two domains maintain a roughly antiparallel alignment, indicating that the opening of the pore may occur by pulling the S5 helix away causing the S6 helix to follow.
....Then it gets to be deep stuff with an astounding amount of detail/diagrams on the workings or potential workings of the Kvs' involved. I mean, I think they know more about this esoterica than I know about what's in a tortilla!

And so on...

Thanks again @locoyeti for going at the hard core part.

Zimichael

 

[1MW]

The last 2 days i had slight edema in my hands and foots and my weight increased.
I got exams for creatinine clearance & BUN and was increased indicating renal pre/failure.
Before taking trobalt these exams was ultra clear with none sign of renal problem.
So be careful with retigabine do exams for renal function once every 10 days to be sure that all are ok.

 

[Moha94]

This is very serious ?