Retigabine (Trobalt, Potiga) — General Discussion

[Grace]

OMG @benryu I just about peed in my pants reading your latest visual/verbal extravaganza...Almost makes it worth having T just to be so educationally entertained!
Now how to edit it so my doc can see the wizdum within and not be blinded by the hilarious light.

SO GREAT to have you aboard!

Zimichael

Ya it almost made me pee myself too. Hes too funny! Lol but sooo smart and convincing... I cant really complain too much cause i just re-read what he has wrote and it makes me feel better ( about T) and future research. Really is an eye opener and makes total sense to me so i have tons of hope now rather then before!

 

[benryu]

@bedouin I do not appreciate my arguments being called rantings, I am all for these drugs and development but there seems to be lacking evidence showing that there is a permanent solution. I am mildly critical of what seems like overt optimism about this issue.

@benryu I appreciate your detailed explanation but has this been demonstrated and proven as fact on humans in practice or is it a theory? And btw did you just call members of this forum, and it seems you are talking about @cdog idiots for theorycrafting about their illness and possible solutions?!

I have seen many papers proving and even microscopically showing one effect of a certain drug and than when I took it, it had the exact opposite effect ruining my health.

No I called the theories I read above "crazy" because they are as crazy as not suported by scientific evidence.
Yes the mechanisms above were confirmed on human, and it has been documented for the last 20 years with numerous articles. ==> google is your friend.

For the "idiots" comment, in case you did not notice, the post is second degree humor. I don't think someone believe here they will die of T. & diarrhea together because some synaptic explosion. I think it was important to close the sane regrowth idea in an humorous way.

@cdog

There is no sub-step here

I really can't make it more accessible than this, maybe read again or maybe if I put it an another way....

glutamate excitotoxicity -> destruction of postsynaptic bouton-> overabundance of glutamate --> over-expression of NMDA glutamate receptors change the structure of the dendrite that's regrowing --> the dendrite altered structure cause synaptic changes of kv3.1 channel--> kv3.1 channel (partially) locked (not screwed up, it's here, just locked)

@@Johno We're all excited for you! But I probably wouldn't include all those supplements. It might be useful to get a pure reading with just the Trobalt.

Totally agree with @jazz , that's a lot of suppelements, and I don't see any reason to do it if it's just for your T., especially since your liver will have hard time with the retigabine, I suggest you don't take as much. Maybe discuss this with your doctor.


PS All: my activity on the forum is going to be very limited in the comming days, and near 0 in september as I take some holidays

 

[cdog]

glutamate excitotoxicity -> destruction of postsynaptic bouton-> overabundance of glutamate --> over-expression of NMDA glutamate receptors change the structure of the dendrite that's regrowing --> the dendrite altered structure cause synaptic changes of kv3.1 channel--> kv3.1 channel (partially) locked (not screwed up, it's here, just locked)

The bolded part above is what requires explanation. Here we have a neuron, and the subcellular location of Kv channels

Figure 5. Subcellular localization of voltage-gated K+ channels Somatic Kv channels include Kv3 and ERG, but the major part of the conductance arises from channels in the axon initial segment (AIS) which are dominated by Kv1, Kv2 and Kv3 channels (as well as voltage-gated sodium channels, Nav). The location of Kv4 on dendrites is implied from their absence in MNTB somatic membrane and evidence from other cell types. Nodes of Ranvier (NOR) contain Nav and Kv3, with Kv1 channels in the juxtaparanodal region, under the myelin sheath (Wang et al. 1993). The last NOR of the axon known as the heminode is particularly large for the Calyx (Leão et al. 2005) and contains Kv1 and Kv3 channels, with the majority of Kv3 being on the non-release face of the synaptic terminal.

So basically all of the Kv channels, including Kv3 are located on the axon & soma, and not on the dendrides. So even if the dendrites change structurally in response to glutamate levels, that should only affect things like passive transmission properties of dendritic input, etc. But how does any of that affect (i.e. make less efficient) the Kv3 channels on the soma/axon? That's the question which needs answering.

Neuroplasticity (particularly long term potentiation via dendrite restructuring) might explain how the neuron changes its spatial and temporal signal summation properties. But it does not explain how/why the actual potassium voltage gated channel becomes down regulated. If we knew how, then we would have much more clarity on how to reverse it.

 

[benryu]

@cdog I like you enthousiasm and motivation, but you don't know when to stop, do you lol?
Seriously even with a lot of efforts I don't understand nor your point nor your question here. *__*

Dude synapse are in 2 parts like talkie walkie emetor & receptor, if one if not working you just can't communicate.
Plus one part strutruce affecting the other, especially during restructuration

Don't bother answering back or asking more

Let's all go back to the retigabine thread, I won't reply to any other off topic questions (sorry ). I am gonna work on an aggregation of most stuff I posted, it will be the right place to discuss and challenge.

 

[cdog]

Seriously even with a lot of efforts I don't understand nor your point nor your question here. *__*

Sorry, I don't know if I could have made it more clear. I'm just trying to get to the bottom of things in terms of understanding. I'm not trying to challenge just for its own sake.

, I won't reply to any other off topic questions (sorry ).

Retigabine works on improving 'locked' Kv channels. I was trying to understand exactly how Kv channels get 'locked'. I think that's pretty "on topic". But I do agree that it should probably be discussed in another thread, and leave this one to user experiences.

 

[SoulStation]

Sorry, I don't know if I could have made it more clear. I'm just trying to get to the bottom of things in terms of understanding. I'm not trying to challenge just for its own sake.

Retigabine works on improving 'locked' Kv channels. I was trying to understand exactly how Kv channels get 'locked'. I think that's pretty "on topic". But I do agree that it should probably be discussed in another thread, and leave this one to user experiences.

Here's a question, what does Retigabine do to help epileptics? How does the potassium channel stuff get affected by Epilepsy ?

 

[russiancarl]

Well this is certainly a long and interesting read. I'm glad I perused it.

I really think we need to get a neuroscientist in here though just wow so many questions!

From what I understand the two people who have been taking this both had their T caused by anti-depressants right? And these are notorious for messing with your GABA receptors? And perhaps these medicines help to fix and regulate those?

Does that mean it may not work for the rest of us without that type of damage or that it possibly still could? Or that possibly it's still in a localized area of the brain that does affect the auditory system and could help us all?

This also makes me wonder about other drugs that supposedly help T. I'm not sure if it's ok to post here but I've heard a lot of people say that MDMA makes it go away. Does anyone know how that drug interacts with the brain? I understand it releases a lot of serotonin and makes you go happy happy but does it mess with the potassium channels like the kv3 or kv1-7 as these drugs do too?

 

[locoyeti]

your presence will be missed @benryu, hope you enjoy the waves. I have one question for you before you leave, if you get a chance: what are the reasons you believe that the blue pigment is methemoglobin? is its reversibility going to involve traditional methemoglobin treatment like methylene blue?

 

[RichL]

It is not offtopic as many here are talking about a solution that will cure them. I am expanding upon the concept. I am saying that our potassium channels are in at least a portion of it permanently damaged and that we are generations away from something that will fix it. For now we can probably remove the tinnitus with various pills but not remove the defect that causes it. The whole point is that there is no trade-off. The concept that life is balanced is a lie. If our evolution was any better we would have intelligence and valuable properties which we lack. The thing is that we are not evolving ourselves we are only evolving a specific fraction of the tools in our daily usage.

This seems to be your opinion based on little or no scientific evidence? (or at least none that you have presented)

Now please can you guy's keep this thread to the given topic, It's getting very hard to follow it when most posts are being added overnight (pacific time) for me and are rapidly fading into another topic!

@benryu has supplied us with more than enough scientific facts (backed by links to peer reviewed literature) to answer every conceivable question that we may have thought of.

Rich

 

[111]

Here's a question, what does Retigabine do to help epileptics? How does the potassium channel stuff get affected by Epilepsy ?

www.tga.gov.au/word/auspar/auspar-retigabine-131017.docx

If you read the above document Soulstation it will basically tell you everything about this product, how it works, what it does, side effects, you name it the info is here. This is GSK's submisson to have this product registered so is very detailed, the line i find interesting is the below statement on page 28, point 3, of this document, looks like they might have had a idea but didnt pursue it further during testing. Have a read it is very informative and interesting

In vitro data suggested that retigabine may interact with KCNQ channels in the inner ear, but this was not addressed in in vivo animal studies.

 

[sticky]

Following @111's post, and for any other Aussie's down here:

Called GSK today, Trobalt not available in Australia yet (which we knew) and could not give me a time frame.

Hopefully we can see it in the near future.

Peace and quiet to all.

Sticky

 

[RichL]

Following @111's post, and for any other Aussie's down here:

Called GSK today, Trobalt not available in Australia yet (which we knew) and could not give me a time frame.

Hopefully we can see it in the near future.

Peace and quiet to all.

Sticky

I'm in NZ and if I can get a doctor to prescribe it then a pharmacist is able to bring it into the country, I would assume it would be the same in Australia?

 

[sticky]

Interesting, thanks RichL!

 

[111]

I'm in NZ and if I can get a doctor to prescribe it then a pharmacist is able to bring it into the country, I would assume it would be the same in Australia?

I will ask the pharmacist that question Rich, i know when i asked my Dr about getting it myself from the int pharmacy with a prescription she would need to write for me, she could not do that, so i will enquire first to see if this is possible and give the info out.

 

[111]

I'm in NZ and if I can get a doctor to prescribe it then a pharmacist is able to bring it into the country, I would assume it would be the same in Australia?

Are you going to do this Rich at all to get it yourself ?

 

[RichL]

Interesting, thanks RichL!

Welcome!

I will ask the pharmacist that question Rich, i know when i asked my Dr about getting it myself from the int pharmacy with a prescription she would need to write for me, she could not do that, so i will enquire first to see if this is possible and give the info out.

I contacted pharmac here in NZ and they gave me all the info I was after, If you contact your equivalent over there they should be able to tell you if you can do the same.

Rich

 

[RichL]

Are you going to do this Rich at all to get it yourself ?

I probably will try but I want to wait and keep an eye on @Mpt and see what happens when he tapers off the drug, I am a bit weary tho so I'll play the wait and see game.

Rich

 

[111]

I probably will try but I want to wait and keep an eye on @Mpt and see what happens when he tapers off the drug, I am a bit weary tho so I'll play the wait and see game.

Rich

does anyone know where Mpt is at these days, same dose or has he reduced it, any news at all ?

 

[Christian_B]

I've seen more and more people wanting to take retigabine/trobalt, but which there T. came from hearing loss or medication withdrawal.

I still don't know how i've got mine, maybe some TMJ issue..

But what is the thoughts that a drug like this or AUT00063 can help my T. as well than people who knows where there T. came from?

My symptoms:

Mostly T. in left ear only
can be low, medium and high pitched (mostly low-medium)
Clicking in ears when using my jaw (mostly left)

I don't know if this tells anything about my specific T...

 

[Christian_B]

does anyone know where Mpt is at these days, same dose or has he reduced it, any news at all ?

As far as i know, he is currently on 900mg/day

 

[undecided]

Another point...even though Retigabine is a blunt instrument (shotgun) and is not laser guided to Kv3, it still seems to be having an effect on our two main guinea pigs so far...Matt and Christian. Of course, the more folks we have trying it the better, especially "long term T'ers" to see how it deals with an 'entrenched' brain functioning pattern.

Also the next big question is what happens when they taper or stop. Now THAT is going to be very intriguing

Honestly, I wouldn't be that concerned about that.
Let's say, for argument's sake, that the drug wears off, say, after 2 weeks (I'm just throwing random numbers around here, obviously).
Tinnitus would come back to it's baseline.
HOWEVER, would that mean a damn thing? You would have a treatment, some SOLID means to help you with the tinnitus, if and when you really needed it.

I believe that the biggest anxiety factor for people with tinnitus is the fact that there is no proven treatment that would alleviate their symptoms, even temporarily.
Therefore you might use the retigabine as required. To help with habituation, to help during a tough period, through some personal problems or whatever. You would define the extent of its usefulness, be it a lifetime commitment or a temporary relief.
It would be a benzo-like treatment with the added benefit of lowering the T.

So, being wary of the side-effects, I'd personally use it for short periods of time on a need-to-use basis. But that's just me.

 

[Carlos1]

I've seen more and more people wanting to take retigabine/trobalt, but which there T. came from hearing loss or medication withdrawal.

I still don't know how i've got mine, maybe some TMJ issue..

But what is the thoughts that a drug like this or AUT00063 can help my T. as well than people who knows where there T. came from?

My symptoms:

Mostly T. in left ear only
can be low, medium and high pitched (mostly low-medium)
Clicking in ears when using my jaw (mostly left)

I don't know if this tells anything about my specific T...

Christian I have the exact same symptoms as you I have had TMJ surgery am I still have T. I too would like to know how and if AUT00063 can help TMJ related T.
@benryu I'd like to thank you for all your info....any thoughts on Christian and my question?
Have a great vacation

 

[111]

I'm in NZ and if I can get a doctor to prescribe it then a pharmacist is able to bring it into the country, I would assume it would be the same in Australia?

asked at the pharmacist and they only get their medications from their australian supplier, so they told me i could not get it supplied this way

 

[benryu]

@Christian_B first it's a bit out of my area of expertise, I am quite confortable with the brain, but I did not work much on any other area of the body

So from my perspective I don't recall any article showing that TMJ can cause excitotoxicity. (Anyone found something about this ?)

It's kind of a good and bad news at the same time I guess.

The bad is that without ototoxicity I doubt the AUT00063 may work on you.

The good is that it's most likely mechanical (jaw pressure on an auditory related area), and is VERY likely curable with conventional medicine (surgery, reajustment, etc...) have you done a scan to check up the jaw ?

@Carlos1 , same comment applies for you

Let's not polute this thread with off topic discussion, feel free to reply with PM (I might be slow to answer tho^_^)

 

[Grace]

@Christian_B first it's a bit out of my area of expertise, I am quite confortable with the brain, but I did not work much on any other area of the body

So from my perspective I don't recall any article showing that TMJ can cause excitotoxicity. (Anyone found something about this ?)

It's kind of a good and bad news at the same time I guess.

The bad is that without ototoxicity I doubt the AUT00063 may work on you.

The good is that it's most likely mechanical (jaw pressure on an auditory related area), and is VERY likely curable with conventional medicine (surgery, reajustment, etc...) have you done a scan to check up the jaw ?

@Carlos1 , same comment applies for you

Let's not polute this thread with off topic discussion, feel free to reply with PM (I might be slow to answer tho^_^)

What about noise induced?!!!!!!! My T isnt from ototoxcoty--- you mean noise induced and ottoxcity right?

 

[Hengist]

What about noise induced?!!!!!!! My T isnt from ototoxcoty--- you mean noise induced and ottoxcity right?

Relax girl, noise creates overexertion of cells that makes ototoxic enviroment. So noise fits in general into ototoxic potassium cathegory.

 

[Martin69]

Mine was not noise-induced, but stress-induced.
But maybe it was noise-induced since my kids are very loud.
And this caused my stress over a long period resulting in T. And I definitely have hearing loss in high frquencies - like more or less everyone at the age of 45.

Before I now freak out that the drug does not work on me, let's see if it works at all and who will be the lucky ones.
Thanks benryu for your excellent work.
And thanks to mpt and christian reporting here.
But we all need to be careful not being too enthusiastic.
On the other side, hope is always good.

 

[benryu]

What about noise induced?!!!!!!! My T isnt from ototoxcoty--- you mean noise induced and ottoxcity right?

Yes, ototoxicity can be caused by noise, drugs or stress.

EDIT: basically most of T. should be tackle (theorically) by AUT00063 providing it works as expected.
The T. not directly curable by this (TMJ, tumor, edema as eg) are curable if the initial problem is fixed. (eg, if you can get a surgery to remove the tumor, the T. will be gone)

 

[Grace]

Okay i was confused because usually everyone uses the term " noise induced" or " ototoxcity" which i thought ment drug induced but okay i get it now. Thanks.

Relax girl, noise creates overexertion of cells that makes ototoxic enviroment. So noise fits in general into ototoxic potassium cathegory.

 

[Hengist]

Okay i was confused because usually everyone uses the term " noise induced" or " ototoxcity" which i thought ment drug induced but okay i get it now. Thanks.

NP, I responeded immedately so you do not panic and increase you tinnitus :3