Retigabine (Trobalt, Potiga) — General Discussion

[jazz]

I've solved problem of kidney stones. On 30 August i will retry starting with 50x3. Hoping...
Ivan

Thank you for the update! Yes, keep us informed!!!

 

[Hudson]

I've solved problem of kidney stones. On 30 August i will retry starting with 50x3. Hoping...
Ivan

I'm scheduling an appointment with a neurologist to see what I can do in terms of obtaining retigabine (potiga in the US).

 

[cdog]

After an acoustic trauma, or after taking some drugs such as quinine there is an interference with the excitability of spiral ganglion neurons (The evil glutamate is guilty ). The membrane potential changes and the modification of the action-potential waveform induced by the problem put the individual in a T. state.

This is still where I'm very unclear. What is the nature of the interference with the excitability of spiral ganglion neurons? Here's a chain of causes :

1. Glutamate excitotoxicity in the hair cell, or even possibly further downstream in spiral ganglion neurons, leads to
2. ???, leads to
3. Down regulation of Kv channels (supposedly Kv3), leads to
4. Potassium isn't diffused out as fast/as well by Kv channels, so membrane potential characteristics change (i.e. becomes less polarized and so more excitable), and also action-potential becomes longer lasting, more bursty.

Big question is - what's #2? Why is this a big question in my view? Because knowing how Kv channels get broken/down regulated/etc. will tell us if that is reversible and perhaps tell us how to reverse it. For example, if they get down regulated to compensate for the lack of signal from a (dead) hair cell, then going on a medication that will up regulate (i.e. modulate) the channel seems like it will only be a patch - when you discontinue the medication, the channels will again compensate back to being down regulated (since the hair cell input will still not be there).

What I'm trying to get at is that answering the very important question of whether drugs like AUT00063 will be something you will permanently have to take or whether they will restore pre-tinnitus functioning of the channels, depends on understanding the nature of how the channels get broken in the first place.

The impact of retigabine on Kv3 is not necessary related to dosage but more a "physiological response" to the drug, like a positive externality if u will, I don't want to get in the details of this here YET because it would be 3 or 4 pages of explanations with maybe 10 or 15 concepts we did not cover yet together. I promess I'll do it in a dedicated section when the time is right!

Looking forward! Perhaps all this 'technical' discussion should be taken to another (new?) thread, so that people who don't want to read it here, don't have to.

 

[dan]

"Anyone who doesn't think it's potentially a very dangerous thing to be messing around with is kidding themselves."

First of all, nobody here is "messing around".
Second one has to weight the risk vs. reward.

So i tried to get trobalt to trial it out. My dr had no issues with me taking it at all off label, she was even pleased to try to help me out, as long as i saw her each week in the first month or so so she could monitor its progress she agreed to me being on it. Then when she went on the system to get it for me, turns out the med has been approved by this countries medical board for release over a year ago but GSK havent marketed it yet here... frustration.. ?

So given the fact that i cannot get this yet, she is more than happy for me to try something else out, so, as i am very very down at the moment in myself, has anyone tried the below med, just wondering if this could help me out ?


Carbamazepine

Abstract
Objectives: There is strong evidence in the literature about the effect of local anesthetics such as lidocaine in controlling tinnitus; these agents act by stabilizing hair cell membrane and cochlear nerve fibers. However, the effect of intravenous lidocaine is transient, and its oral analog (tocainide) does not have the same efficacy for long-term treatment in patients with tinnitus. Some oral anti-epileptic drugs (carbamazepine, for instance) have been used alternatively in several studies.

The mechanism of action of carbamazepine and its derivatives is relatively well-understood. Carbamazepine stabilizes the inactivated state of Voltage-gated sodium channels, making fewer of these channels available to subsequently open. This leaves the affected cells less excitable until the drug dissociates.[citation needed] Carbamazepine has also been shown to potentiate GABA receptors made up of alpha1, beta2, gamma2 subunits.[27] This mechanism may contribute to its efficacy in neuropathic pain and manic-depressive illness.

If you're worried about Troblat, you should be very scared to take Carbamazepine (Tegretol).
It has a really nasty side effect profile to the point that a patient needs monthly blood screenings of white blood cell count and semi annual liver function.
Personally, I think vilifying Trobalt sounds silly, since there are other even more scary drugs out there which are approved and used routinely.

 

[111]

Dan, i think you have confused my statement with someone elses, could i suggest you read what i have said, i wanted to get on this stuff and today would have been my first day on trobalt, but it isnt available yet so i could not get it, so i was asking about Tegretaol as an alternative, where was i vilifying Trobalt please ?

 

[Christian78]

How's your tinnitus today, Christian?

This morning when i woke it was strong, i used some mix of high sound (I dont know can be uploaded) but it is super, it is nice day, t on 8% for now

 

[dan]

Dan, i think you have confused my statement with someone elses, could i suggest you read what i have said, i wanted to get on this stuff and today would have been my first day on trobalt, but it isnt available yet so i could not get it, so i was asking about Tegretaol as an alternative, where was i vilifying Trobalt please ?

Sorry mate, I read Carbamazepine and for some reason thought you were someone else. Forgive me, this thread is so confusing. What I wanted to say to you was the Carbamazepine was not found to be very effective for treating tinnitus, and I'm not surprised because we want potassium targets, not sodium.
I think you should not give up on Trobalt that easy just because its unavailable in your country - I'm certanily not giving up. Good luck.

 

[Christian78]

@Christian78 - so was it only yesterday you were without tinnitus or has it come back? i don't understand..

During a sleep it goes up, become i take a pill 22:00 and go up with my masking sounds, and terrible upper back pain (probably i move to little, have to do exercise more- stretch , at parents i had it little, here 6 times more, i don't know why, i have been painting walls yesterday), took a pill at 10:00 (12 h distance, so what happen is that pill fell in to low concentration in blood. So, bow is 6% of sound of t, but it varieties with stress it go up but still tolerable - habituated.

I think you can drop message to my skype christian.davidson

Red is normal concentration when you ideally take pill every 8 h, but with me i sleep and before a sleep i take pill so it has some spikes sometimes it gets to 500 mg in blood, other it falls to 130 mg.

 

[dan]

Heck I'd take 6% !!! Happy for you man. Let's see how many others can benefit.

 

[Hengist]

So i tried to get trobalt to trial it out. My dr had no issues with me taking it at all off label, she was even pleased to try to help me out, as long as i saw her each week in the first month or so so she could monitor its progress she agreed to me being on it. Then when she went on the system to get it for me, turns out the med has been approved by this countries medical board for release over a year ago but GSK havent marketed it yet here... frustration.. ?

So given the fact that i cannot get this yet, she is more than happy for me to try something else out, so, as i am very very down at the moment in myself, has anyone tried the below med, just wondering if this could help me out ?

What country are you in?

 

[111]

G'day Hengist... i am from the land down under... Australia...

 

[111]

Sorry mate, I read Carbamazepine and for some reason thought you were someone else. Forgive me, this thread is so confusing. What I wanted to say to you was the Carbamazepine was not found to be very effective for treating tinnitus, and I'm not surprised because we want potassium targets, not sodium.
I think you should not give up on Trobalt that easy just because its unavailable in your country - I'm certanily not giving up. Good luck.

Hi Dan, no worries, thought you got mixed up. i would really like to trial this, but i dont know why GSK have had approval now for around 12 months, yet it is still not available here, i have even called their head office here and asked when it will be released but you get no answers from them. I did ask about getting it from the internationl pharmacy but my GP was too keen on doing that, and i am sure there are some rules around doing things like this which the GP's need to comply with i suppose. I might see if i can get it that way again though, nothing to lose by asking again i suppose.

 

[Johno]

For example, if they get down regulated to compensate for the lack of signal from a (dead) hair cell, then going on a medication that will up regulate (i.e. modulate) the channel seems like it will only be a patch - when you discontinue the medication, the channels will again compensate back to being down regulated (since the hair cell input will still not be there).

Compensation of missing signal? Oh yes, i read about it many times, but i dont believe this. Is there some reason to compensate it? No. Another unproven theory (shit). Tinnitus is an issue, not mechanism to repair (in this reason by compensation) some damage.

 

[sticky]

Woah! @111,

I am in Australia too and have recently stumbled across this forum. (have been on the Tinnitus support message board and RNID, Daily Strength.) I am credible

I went to the pharmacy today and Trobalt is not available in Australia.

I will be looking to see a nuerologist, GP to see how tangible it is for me to get Trobalt, maybe you have already done this? I might PM you later

Sticky

 

[Hengist]

This is still where I'm very unclear. What is the nature of the interference with the excitability of spiral ganglion neurons? Here's a chain of causes :

1. Glutamate excitotoxicity in the hair cell, or even possibly further downstream in spiral ganglion neurons, leads to
2. ???, leads to
3. Down regulation of Kv channels (supposedly Kv3), leads to
4. Potassium isn't diffused out as fast/as well by Kv channels, so membrane potential characteristics change (i.e. becomes less polarized and so more excitable), and also action-potential becomes longer lasting, more bursty.

Big question is - what's #2? Why is this a big question in my view? Because knowing how Kv channels get broken/down regulated/etc. will tell us if that is reversible and perhaps tell us how to reverse it. For example, if they get down regulated to compensate for the lack of signal from a (dead) hair cell, then going on a medication that will up regulate (i.e. modulate) the channel seems like it will only be a patch - when you discontinue the medication, the channels will again compensate back to being down regulated (since the hair cell input will still not be there).

What I'm trying to get at is that answering the very important question of whether drugs like AUT00063 will be something you will permanently have to take or whether they will restore pre-tinnitus functioning of the channels, depends on understanding the nature of how the channels get broken in the first place.



Looking forward! Perhaps all this 'technical' discussion should be taken to another (new?) thread, so that people who don't want to read it here, don't have to.

http://qjmed.oxfordjournals.org/content/93/12/787.full

I have read this article and it seems that potassium is related to a lot of nerve signal missfunction and that some other diseases are based on.

The early reports of the presence of anti‐potassium channel antibodies in the serum of patients with neuromyotonia were based on an immunoprecipitation assay.
...In summary, therefore, patients with acquired neuromyotonia harbour antibodies directed against voltage‐gated K+ channels. These antibodies reduce the K+current conducted by these channels and thus lead to a prolongation of the nerve action potential. This results in increased neurotransmitter release that manifests clinically as muscle hyperexcitability

I think that if some damage can make your body permanently have antibodies within your nerves that all they do is make your nerves missfunction, our bodies are pathetic and geared towards being weak and staying crippled once they are damaged. I do not share the rosy view that any medicine will fix our hearing nerves, as this is a illness that in most cases is something you die with it only seems logical that a non-permenent solution that you also seem to need to take until you die is the only thing that will fix it. Simply, mammalian bodies are stubborn not to regenerate. I know this from personal experiance, there has not been a single injury I have fully healed from.

 

[Hengist]

Hi Dan, no worries, thought you got mixed up. i would really like to trial this, but i dont know why GSK have had approval now for around 12 months, yet it is still not available here, i have even called their head office here and asked when it will be released but you get no answers from them. I did ask about getting it from the internationl pharmacy but my GP was too keen on doing that, and i am sure there are some rules around doing things like this which the GP's need to comply with i suppose. I might see if i can get it that way again though, nothing to lose by asking again i suppose.

How did you approach your neurologist about getting retigabine, did you just ask for it or did you present any papers confirming the efficacy?

 

[bedouin]

What I'm trying to get at is that answering the very important question of whether drugs like AUT00063 will be something you will permanently have to take or whether they will restore pre-tinnitus functioning of the channels, depends on understanding the nature of how the channels get broken in the first place.

All good theoretical questions but i'm not really bothered if I have to take it for the rest of my life for now. I'm sure if they can figure out a way to stop it now with a pill a day, in time they can figure a way to stop it with one pill. As long as AUT63 stops it, i'll take it every day. Then I can have my life back. If it makes it to market it should be side effect free but we'll only know that in the long term, like Retigabine and it's 4years+ side effects.

 

[bedouin]

our bodies are pathetic and geared towards being weak and staying crippled once they are damaged

I don't agree with that. The human body is the most complex organism on the planet and has the ability to regenerate, just not in the case of T, which I am as bummed about as everyone else with T. However, I have seen stroke victims recover from paralysis, one side of the brain compensating for the other and many cases of such miraculous recovery, sometimes from sheer will power of the individual. The fact that we don't have the regenerative inner ear hair cell recovery of chickens does not label our bodies as pathetic.

 

[bedouin]

So, bow is 6% of sound of t, but it varieties with stress it go up but still tolerable - habituated

That is great news Christian. Please keep us updated on your progress.

 

[Hengist]

I don't agree with that. The human body is the most complex organism on the planet and has the ability to regenerate, just not in the case of T, which I am as bummed about as everyone else with T. However, I have seen stroke victims recover from paralysis, one side of the brain compensating for the other and many cases of such miraculous recovery, sometimes from sheer will power of the individual. The fact that we don't have the regenerative inner ear hair cell recovery of chickens does not label our bodies as pathetic.

Not really, except for our intelligence, nothing makes us special and the ability to regenerate has not been demonstrated in anything except liver. People recover some function but that is not regeneration of damaged properties it is usually only scar tissue that is either not pushed to perform like healthy tissue is or not tracked long enough to show it's true weak properties. There are always remarkable stories about something that was predicted to be far worse turning out better but that is usually just bad diagnostics or that person has exceptioanlly good genes with little to no predisposition towards toxic and inflammatory accumulation. Compare that with all the people who idiopathically get inflammatory and auto-imune illnesses out of nothing. You only need to track how professional athletes who get injuries never heal them, and they always re-surface again and how people with chronic illness which has any inflammatory properties only get worse unless there are some chemotherapy-for-life stuff. The whole human-body-is-a-wonderfull-perfection is just a joke. Apes have like 3 times muscle power per kilogram of muscle than us lol and that is only one example.

 

[111]

How did you approach your neurologist about getting retigabine, did you just ask for it or did you present any papers confirming the efficacy?

Hi Hengist, i basically went to my Dr, who is very good, and the conversation was along the lines of............ Dr, there is this new medication out there that has worked on people, can i try it, she asked me what it was, she did a quick look at some paper on it and said, yes, lets prescribe it off label, what have you got to lose. She then said i would need to see her each week for at least two months to monitor any side effects, which i said was a good idea, but then we found out it is not availabe yet, so thats my stumbling block at the moment. She did say the next time a rep from GSK calls in she would enquire about when it will be released, so i am just hoping it wont be long as it got approval around 12 months ago to be used, its just not been released to the market yet. So thats basically how it happend for me.

 

[SteveToHeal]

Not really, except for our intelligence, nothing makes us special and the ability to regenerate has not been demonstrated in anything except liver. People recover some function but that is not regeneration of damaged properties it is usually only scar tissue that is either not pushed to perform like healthy tissue is or not tracked long enough to show it's true weak properties. There are always remarkable stories about something that was predicted to be far worse turning out better but that is usually just bad diagnostics or that person has exceptioanlly good genes with little to no predisposition towards toxic and inflammatory accumulation. Compare that with all the people who idiopathically get inflammatory and auto-imune illnesses out of nothing. You only need to track how professional athletes who get injuries never heal them, and they always re-surface again and how people with chronic illness which has any inflammatory properties only get worse unless there are some chemotherapy-for-life stuff. The whole human-body-is-a-wonderfull-perfection is just a joke. Apes have like 3 times muscle power per kilogram of muscle than us lol and that is only one example.

It is a bit off topic but perhaps no regeneration but load balancing - it still has the ability to correct itself in some instances and not others through different processes. I'd much rather have human intelligence than ape muscles I think the term perfectly imperfect comes to mind but can be equally as frustrating to come to terms with and accept. I am not prepared to accept I will have loud and annoying T for the rest of my life. I would rather try again next life than live out my days in this broken speaker "ON" state.

 

[111]

Woah! @111,

I am in Australia too and have recently stumbled across this forum. (have been on the Tinnitus support message board and RNID, Daily Strength.) I am credible

I went to the pharmacy today and Trobalt is not available in Australia.

I will be looking to see a nuerologist, GP to see how tangible it is for me to get Trobalt, maybe you have already done this? I might PM you later

Sticky

No worries mate, speak soon eh....

 

[Hengist]

Hi Hengist, i basically went to my Dr, who is very good, and the conversation was along the lines of............ Dr, there is this a new medication out there that has worked on people, can i try it, she asked me what it was, she did a quick look at some paper on it and said, yes, lets prescribe it off label, what have you got to lose. She then said i would need to see her each week for at least two months to monitor any side effects, which i said was a good idea, but then we found out it is not availabe yet, so thats my stumbling block at the moment. She did say the next time a rep from GSK calls in she would enquire about when it will be released, so i am just hoping it wont be long as it got approval around 12 months ago to be used, its just not been released to the market yet. So thats basically how it happend for me.

How is it not available? I mean you have a desire to buy it, what stupid law is preventing you, I thought that Australia has one of the freest markets why do they have to "market" it for that specific use, just make your doctor write you have epilepsy or something. Bad laws are meant to be broken.

It is a bit off topic but perhaps no regeneration but load balancing - it still has the ability to correct itself in some instances and not others through different processes. I'd much rather have human intelligence than ape muscles I think the term perfectly imperfect comes to mind but can be equally as frustrating to come to terms with and accept. I am not prepared to accept I will have loud and annoying T for the rest of my life. I would rather try again next life than live out my days in this broken speaker "ON" state.

There is functional recovery but not regeneration and it is not the same thing. My point is not that there is a tradeoff between strenght and intelligence but that the properties that we have are rather weak, gram-per-gram we could be much healthier, capable of tolerating and dealing with more extreme enviroment. Evolutionarly we are fairly trashy and require extreme maintainance just for sub-optimal functionaing (meaning if you push yourself close to 100% in any area that area you will have permanent damage). Just look at some amphibians and reptiles how they can handle almost anything with no care whatsoever without ever getting sick and living past 100 years.

 

[SteveToHeal]

There is functional recovery but not regeneration and it is not the same thing. My point is not that there is a tradeoff between strenght and intelligence but that the properties that we have are rather weak, gram-per-gram we could be much healthier, capable of tolerating and dealing with more extreme enviroment. Evolutionarly we are fairly trashy and require extreme maintainance just for sub-optimal functionaing (meaning if you push yourself close to 100% in any area that area you will have permanent damage). Just look at some amphibians and reptiles how they can handle almost anything with no care whatsoever without ever getting sick and living past 100 years.

Sure - but they live in the mud. I know what you are saying but i doubt we are going to change the grand design by complaining about it. This is a debate on evolution and probably needs a separate thread or at least has a home in the "Regeneration" or "Stem Cell" thread.

For the record I do agree with your comment re the complexity trade-off. We just weren't blessed with that gene. Instead, we were given the ability to use remote controls ... something amphibians would struggle with

 

[bedouin]

Thankyou @Markku , @Johno , for Trobalt prices.

Anybody in UK can check?

I will check

 

[Hengist]

Sure - but they live in the mud. I know what you are saying but i doubt we are going to change the grand design by complaining about it. This is a debate on evolution and probably needs a separate thread or at least has a home in the "Regeneration" or "Stem Cell" thread.

For the record I do agree with your comment re the complexity trade-off. We just weren't blessed with that gene. Instead, we were given the ability to use remote controls ... something amphibians would struggle with

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.

 

[Johno]

Ok. I have two boxes of Trobalt. 21x50mg and 84x100mg. From now (15.00 Paris time) i decided to join experimental group.

first week 3x50mg, the second one 100mg. I dont know yet, if i increase dosage to 150 or 200mg.

I take per day:
A vit 6000iu, E vit 400iu, C vit 1000mg, Zinc citrate 25mg, 3x500magnesium lactate, 3x600mg NAC, 1x20mg Lutein and 2x betahistine 24 mg
1x5mg melatonin - before sleep
and for now Trobalt.

I will report every changes of T or adverse effect of course.

Short about my T:
Acoustic trauma 6.7. 2012 at 10.30am

multitonal tinnitus in both ears, and white noise type hissing
worsened hearing (with many notches)

 

[rtwombly]

@Johno have you had a baseline eye exam? The suggestion is one before starting, then one every six months.

 

[111]

How is it not available? I mean you have a desire to buy it, what stupid law is preventing you, I thought that Australia has one of the freest markets why do they have to "market" it for that specific use, just make your doctor write you have epilepsy or something. Bad laws are meant to be broken.

It isnt a law stopping me its the fact that there are none of these tables available to get. The medication was approved last year but the supplier of this medication ( gsk ) have not decided on a date when it will be made available here, so thats the reason why i cannot get any, as per below..


TGA registers Trobalt
GlaxoSmithKline has announced the TGA registration of Trobalt (retigabine). The product is not currently commercially available in Australia, with GSK saying it will work with its partner company Valeant to provide certainty as to how Trobalt may be supplied to patients. Trobalt is used for the treatment of epilepsy.
The above snippet is the first part of an article sent to subscribers in Pharmacy Daily's issue from 29 Oct 13