Retigabine (Trobalt, Potiga) — General Discussion

[SoulStation]

yes, i am on 200 mg last 7 days, well i sleep better, i take less sleeping pill and i dont use any clonopopin and i find my self to sleep better, to want to go out, to want to go to gym and i dont know it is strange, sometimes t is stronger sometimes not but not like ordinary t, some days t is in background i dont pay attention on it, it is not intrusive.

It sounds like this is helping you achieve some habituation. Great work. Hope all is well and balanced.

 

[Lisa88]

I have not read this entire thread. Just wanted to put in my two cents.
I have been taking Lorazepam, a benzo binding to the gaba receptors, and which also contains anti convulsive properties. Like these other drugs, it therefore alters brain chemistry.
I have been on .5mg daily for the last 5 months. I am now 9 months into my t. First couple of months taking it, I too could hardly hear my multi tonal t, and reactive t plus fluctuations had evened out also.
But as with any brain chemistry altering drug, tolerance is eventually reached, and the drug will lose its effect. It has started to lose its effect with me. I am trying to wean off of it which is proving difficult and causing louder t.
I regret taking this drug daily. They say that 80% of sudden onset t cases substantially fade naturally within the first year (fade in volume, not just re habituation). I worry I have ruined my chances of this "natural" fading within the apparent 1 year plasticity deadline (a deadline which I understand still has not been proved).
Other friends who started their t around the same time as mine who have amazingly done this drug free have experienced this natural fading.
And I am devastated at my bad decision making.

 

[lapidus]

@Lisa88 Well I think you should read the whole thread. It's a good read. I think it's a difference though, between a benzo and a potassium channel modulator. @benryu has explained very good what the theory is behind potassium channels + T in this thread.

Now I don't really get that 80% thing. Do they mean that 80% of all people who get T get rid of it within a year? Cus that's just total bullshit. If you have had constant T for more than 3 days, then chances are pretty freakin high you'll have chronic T. Or do they mean that the sound just gets a little bit lower within a year?

 

[dan]

She said substantially fade.

 

[Lisa88]

Yes - substantially fade for sudden onset t cases. Not gradual onset t cases. Thanks, will read the whole thread. Hoping that opening the potassium channels can eventually be created by something other than a brain chemistry altering drug with tolerance associated. But will read the thread for more. Thanks.

 

[rtwombly]

Yes - substantially fade for sudden onset t cases. Not gradual onset t cases. Thanks, will read the whole thread. Hoping that opening the potassium channels can eventually be created by something other than a brain chemistry altering drug with tolerance associated. But will read the thread for more. Thanks.

Yeah, this is a totally different thing you're talking about. Different type of drug, different effects. Retigabine is not a medication to be taken lightly, but it is nothing like a benzo. The drug we all hope will work better than Retigabine, AUT00063, will hopefully be free of side effects for l practical purposes.

There is no reason to beat yourself up about taking medication that helped you. It likely had no effect on your tinnitus at all, just happened to coincide with a change in your symptoms, or it helped you sleep, which can make a huge positive difference. That 80% thing is another way a doctor tried to fob you off. It's based on nothing at all, it was just something to say to get you to go away. It's like the statistic I read that the average delay between onset of tinnitus and when people go to a doctor is two years. Two years!?? "Oh, by the way, doc, do you mind having a peek in my ear, it's been ringing for TWO YEARS!" Seriously, who comes up with these numbers?

 

[Lisa88]

Good point @rtwombly
I have yet to actually see statistical or imaging evidence re that 1 year marker of doom and gloom.
Everyone in their first year of t is terrified they are going to miss the boat.

 

[benryu]

Good point @rtwombly
I have yet to actually see statistical or imaging evidence re that 1 year marker of doom and gloom.
Everyone in their first year of t is terrified they are going to miss the boat.

Hey guys for the one who just got in the thread, I have explained several times why time has NO impact on the reversability of T.
Time only matters in the first days maybe weeks for the glutamate saturation, it's tackled by the AM-101.
For the rest of us after the glutamate induced the T. state, time is expected just to add a little inertia to the treatment, but will be as efficient. All recent scientific articles, research & investments point in this direction.

So you could have had T. for 1 year, 10 years or 30 years it won't make much of a difference as long a drug reopen the right potassium channel valve.

(I simplify things a lot, I am not in the mood for my usual long scientific tirade haha, if you want more just go back in the thread or check my posts in my profile <3 )

 

[Christian78]

I have not read this entire thread. Just wanted to put in my two cents.
I have been taking Lorazepam, a benzo binding to the gaba receptors, and which also contains anti convulsive properties. Like these other drugs, it therefore alters brain chemistry.
I have been on .5mg daily for the last 5 months. I am now 9 months into my t. First couple of months taking it, I too could hardly hear my multi tonal t, and reactive t plus fluctuations had evened out also.
But as with any brain chemistry altering drug, tolerance is eventually reached, and the drug will lose its effect. It has started to lose its effect with me. I am trying to wean off of it which is proving difficult and causing louder t.
I regret taking this drug daily. They say that 80% of sudden onset t cases substantially fade naturally within the first year (fade in volume, not just re habituation). I worry I have ruined my chances of this "natural" fading within the apparent 1 year plasticity deadline (a deadline which I understand still has not been proved).
Other friends who started their t around the same time as mine who have amazingly done this drug free have experienced this natural fading.
And I am devastated at my bad decision making.

It is very hard to get of it, fast geting of it creates additional tinnitus, that does not has to stay permanent and it may stay additional on top of your, therefore the safest way to wean of it is safe slow way.

HOW TO WITHDRAW FROM BENZODIAZEPINES AFTER LONG-TERM USE

please read this site, i am sure it might give you help:
http://www.benzo.org.uk/manual/bzcha02.htm

 

[Lisa88]

Thanks @benryu for the info on this thread.
Fascinating stuff.
You say in one of your posts that plasticity could be no more than inertia reversed. But you do say that it matters on a cellular level. Could you expand on that?
Also, in your data research of t and the brain, have you come across any studies or statistics on plasticity as it relates to t?
Doctors across the world must be getting their one year marker from somewhere. Or maybe not

 

[Lisa88]

@benryu
p.s. if the potassium channels are a common denominator for t of all causes, and would work for all time frames, that would be a truly wonderful thing! Maybe you can get your research and data to UCSF and other universities leading research on t.

 

[attheedgeofscience]

They say that 80% of sudden onset t cases substantially fade naturally within the first year (fade in volume, not just re habituation).

I am not sure who "they" is. The biggest factors in determining inner ear tinnitus outcome is related to etiology (acoustic trauma, presbyacusis, ototoxicity, head injury, infection, etc.) and symptomatology (continous ie. 24/7, on/off, decreasing-increasing over time). Sudden onset of tinnitus can occur across a number of etiologies and presents no real baseline reference point in itself. As an example, tinnitus due to presbyacusis can certainly occur suddenly and will almost certainly not go away, whereas tinnitus due to acoustic trauma (eg. gunshot noise) will also present itself immediately, but may well fade away over time (ie. hours/days) as the temporary hearing threshold shift recovers.

 

[benryu]

Thanks @benryu for the info on this thread.
Fascinating stuff.
You say in one of your posts that plasticity could be no more than inertia reversed. But you do say that it matters on a cellular level. Could you expand on that?
Also, in your data research of t and the brain, have you come across any studies or statistics on plasticity as it relates to t?
Doctors across the world must be getting their one year marker from somewhere. Or maybe not

Thanks for the comment.

I am not sure which post you're making a refence to, but I think I was talking about the cellular level for the hair cell degeneration as well as the glutamate "overdose".
Brain plasticity is a very dense area of research with many ramification. Plasticity can be of many types and involve cortical remapping, neural path changes, synaptic repolarization, etc...
It's very hard to get data on t. plasticity, but if your question is how much time does it take to the brain to operate changes (plasticity wise), it's a matter of weeks for a full process.
(eg: http://www.jneurosci.org/content/26/23/6314.abstract)

The one year marker is just an easy marker for everyone and to control the research, it's nothing more than a tool. It does not mean anything.

When Auris will published the AM-101 results what they want to achieve with their study design is to compare groups based on the time they had T.
Based on that they will create a new marker, but I don't expect it to be more than 3 months. Plus it should not supress T., it will maybe reduce it a lot, but not supress it as glutamate will still go through.

This is why the real deal for us is the AUT00063 or other potassium channel oriented medicamentation. It has to be precise (channel wise), tuning will be needed, but I have no doubt that is the solution we have been waiting for, and it's coming soon.

 

[Lisa88]

Thank you both. Yes, different etiologies and different types of plasticity, not to mention the fact that long term patients rarely report their progress to the ENTs/audiologists who supposedly are stating this one year marker, - well this all seems to render that marker invalid.
Yes, looking forward to seeing the next steps in the potassium channel openers. Thank you so much!

 

[SteveToHeal]

Thanks for the comment.

I am not sure which post you're making a refence to, but I think I was talking about the cellular level for the hair cell degeneration as well as the glutamate "overdose".
Brain plasticity is a very dense area of research with many ramification. Plasticity can be of many types and involve cortical remapping, neural path changes, synaptic repolarization, etc...
It's very hard to get data on t. plasticity, but if your question is how much time does it take to the brain to operate changes (plasticity wise), it's a matter of weeks for a full process.
(eg: http://www.jneurosci.org/content/26/23/6314.abstract)

The one year marker is just an easy marker for everyone and to control the research, it's nothing more than a tool. It does not mean anything.

When Auris will published the AM-101 results what they want to achieve with their study design is to compare groups based on the time they had T.
Based on that they will create a new marker, but I don't expect it to be more than 3 months. Plus it should not supress T., it will maybe reduce it a lot, but not supress it as glutamate will still go through.

This is why the real deal for us is the AUT00063 or other potassium channel oriented medicamentation. It has to be precise (channel wise), tuning will be needed, but I have no doubt that is the solution we have been waiting for, and it's coming soon.

Hi benyryu.

Don't mean to hijack this Retigabine thread but ... do you not think AM101 will have much effect on T sufferers > 3 months?

I guess what I am also struggling to understand is how 3 shots of eskatimine can prevent the over-production of glutamate on a permanent basis. Let's say it supresses it as you say. Is that a permanent supression? I see some of the guys on the AM101 thread go back for more shots and maybe that's the reason why they need to return for more shots, as the first 3 shots aren't permanent. How many shots supress it permanently i wonder? And would they supress T > 3 months.

 

[benryu]

Hi benyryu.

Don't mean to hijack this Retigabine thread but ... do you not think AM101 will have much effect on T sufferers > 3 months?

I guess what I am also struggling to understand is how 3 shots of eskatimine can prevent the over-production of glutamate on a permanent basis. Let's say it supresses it as you say. Is that a permanent supression? I see some of the guys on the AM101 thread go back for more shots and maybe that's the reason why they need to return for more shots, as the first 3 shots aren't permanent. How many shots supress it permanently i wonder? And would they supress T > 3 months.

Hey Mr Hijacker

I think the sooner the AM-101 is taken, the most effective it will be.
Your confusion comes from the fact that you assume that the excess of glumate is permatent. This is not true, it's very short and the death process of hair cell is matter of week. It was mainly tested on animal models, but it should be very similar for human.
During the death process the excess of glutamate is being released but will go back to a normal level when hair cells are back on normal degenerative pace.

Basically the AM-101 is not here to prevent the production but acts as a net to catch and block the glutamate and prevent it to cause too much otoxicity.

For the number of shots, I think this article will give you a good parallel:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053280#pone.0053280-Ohtani1

However, we found that the cochlea had a remarkable ability to recover in the face of continued HPβCD dosing. The recovery precludes hair cell loss as a mechanistic explanation behind threshold shifts that peak around 7 weeks, since the mammalian cochlea is unable to spontaneously regenerate sensory hair cells.

The other way to see the problem is that the amount of "blockers" injected will be consumed over the time and as the hair cell death process can last several weeks. Sometime the initial dose will be enough as a few cells will die, sometimes it's necessary to repeat the operation as bigger quantity of hair cells are dying.

So in conclusion it's unlikely to be efficient after a couple of weeks (months), according to animal models, 3 months is already a generous target.
That being said, I don't think the AM101 will be a sufficient treatment alone in most case, and we are in good track for chronic T. as we identified the trigger: some Potassium channel.
No need to worry, it's cool they found something for acute T., but it's just a first step and chronic T. will also have its traiment soon I believe.

 

[SteveToHeal]

Hey Mr Hijacker

I think the sooner the AM-101 is taken, the most effective it will be.
Your confusion comes from the fact that you assume that the excess of glumate is permatent. This is not true, it's very short and the death process of hair cell is matter of week. It was mainly tested on animal models, but it should be very similar for human.
During the death process the excess of glutamate is being released but will go back to a normal level when hair cells are back on normal degenerative pace.

Basically the AM-101 is not here to prevent the production but acts as a net to catch and block the glutamate and prevent it to cause too much otoxicity.

For the number of shots, I think this article will give you a good parallel:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053280#pone.0053280-Ohtani1



The other way to see the problem is that the amount of "blockers" injected will be consumed over the time and as the hair cell death process can last several weeks. Sometime the initial dose will be enough as a few cells will die, sometimes it's necessary to repeat the operation as bigger quantity of hair cells are dying.

So in conclusion it's unlikely to be efficient after a couple of weeks (months), according to animal models, 3 months is already a generous target.
That being said, I don't think the AM101 will be a sufficient treatment alone in most case, and we are in good track for chronic T. as we identified the trigger: some Potassium channel.
No need to worry, it's cool they found something for acute T., but it's just a first step and chronic T. will also have its traiment soon I believe.

Thanks @benryu . I won't respond with another batch of questions in fear of being labelled Mr Hijacker
Great input as always mate. Tx.

 

[SteveToHeal]

Thanks @benryu . I won't respond with another batch of questions in fear of being labelled Mr Hijacker
Great input as always mate. Tx.

Now back to Retigabine all

 

[lapidus]

So @Mpt and @Christian78 are the only ones currently on this drug right?

@Zimichael are you still with us bud?

 

[undecided]

I'm reading that Retigabine acts on potassium Kv7.2, to Kv7.5 channels.
Amitriptyline, an old but quite common AD, is supposed to act on roughly the same channels (Kv1.1,Kv7.2,andKv7.3)... It would appear that amitriptyline has a rather favourable track record with tinnitus --> e.g here.

Would it be safe to assume that using amitriptyline alongside retigabine would enchance the 'healing' effect on the potassium channels? I'm wondering, since amiptriptyline is a channel blocker and retigabine is a modulator...

I might give amitriptyline a shot for a couple of months, since I'm supposed to be on some sort of anti-depressant (I hardly use them anymore) just to contribute on the scientific side of things!

 

[Cor]

So in simple terms, if you eat sugar, potatoe, pasta, rice or stuff with high carbs, your pancrea gonna release a lot of insulin that will take the glucose and mess with the potassium channels.

@benryu This explains why I get spikes when eating something high in sugar.

@SoulStation can you tell us which literature you took with you? I have a really good psychiatrist (seeing him temporarily after medication induced psych problems) that has T as well, and he works in a hospital. He was very interested in this information.

 

[Christian78]

I'm reading that Retigabine acts on potassium Kv7.2, to Kv7.5 channels.
Amitriptyline, an old but quite common AD, is supposed to act on roughly the same channels (Kv1.1,Kv7.2,andKv7.3)... It would appear that amitriptyline has a rather favourable track record with tinnitus --> e.g here.

Would it be safe to assume that using amitriptyline alongside retigabine would enchance the 'healing' effect on the potassium channels? I'm wondering, since amiptriptyline is a channel blocker and retigabine is a modulator...

I might give amitriptyline a shot for a couple of months, since I'm supposed to be on some sort of anti-depressant (I hardly use them anymore) just to contribute on the scientific side of things!

If you noticed publication was made 2001, it is 13 years ago in "old" Turkey, their investigation showed nothing.I used that one after i got t, Dr said it is good for sleep, but during day t was much higher. If it was so effective they would recommend it to be tried, the side effect is worsening of t.

Therefore I do not trust it. But I wish a luck to you to try it. I tried Lyrica and got 200% raise in lvl of tinnitus, and it is also on recommended list.

 

[Johno]

Chris78, Mpt, how are you? Some good news?

 

[Zimichael]

@lapidus ...yeah, I have just logged on after being "away" (see below) for 10 days. Just re-acclimating to a world that needs earplugs again and lots to catch up on. Will update soon and see where I'm at with Potiga hunt. ~ Zimichael

That is my tent circled in red...Glorious isolation and quiet!!!

 

[Christian_B]

Seriously, i think people using earplugs for 'everyday use' hurt their ears more than save them.. No proof, just my thoughts.

 

[Cor]

Everyday use seems a little excessive, but looking back I wish I had used earplugs more.

 

[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 ).

...

Going back to the potassium channels, Kv7 channels primarily control the interspike interval with a limited effect of the repolarization. Kv3 channels control the repolarization of the action potential and are expected to induce a new state.

Are you saying that there is some causative link between glutamate excitotoxicity and blocked Kv channels? I tried to find this in some articles you linked, but wasn't able to.

[According to one of them ('Katp channels are key modulators of glutamate receptor"), "Increase in glutamate release from the pre-synaptic termini allows repeated neuronal excitation that causes the entry of lethal levels of Ca2+ and leads to glutamate excitotoxicity." (page 3, bottom). It then goes on to say : "The opening of the voltage gated K+ channels is a major component that causes repolarization of the cell to the resting potential. This property allows the neuron to curb calcium influx and thus decrease extensive glutamate release" (page 4, bottom).

This seems to say that the link between glutamate and Kv channels is that activating the Kv channels would be useful (to repolarize the cells back to the resting potential) before the neuronal cell dies. How does this link translate to glutamate blocking Kv channels.]

The idea is to open the right channels to lead to a neuronal hyperpolarization, thereby stabilizing the membrane potential and decreasing excitability.(No or very little Tinnitus)

I'm still learning this (browsing wikipedia, etc. ), but from what I got so far opening (modulating) the Kv channel leads to the outflow of potassium (K+) ions out of the cell, thereby hyperpolarizing the cell - that is, restoring the membrane potential to a "resting potential". So if a Kv channel is blocked, this restoration will not happen, and so it seems that the cell will remain depolarized forever. So it seems like it's the opposite of excitability (overconduction of signal) - the always depolarized neuron should just simply never transmit a signal?

 

[SoulStation]

@benryu This explains why I get spikes when eating something high in sugar.

@SoulStation can you tell us which literature you took with you? I have a really good psychiatrist (seeing him temporarily after medication induced psych problems) that has T as well, and he works in a hospital. He was very interested in this information.

Hey---I basically printed out any evidence I could find on Potassium Channel Modulators and a the effect on noise induced tinnitus and prevention of chronic tinnitus. Most of the articles on Regitabine/Potiga/Trobolt/Ezogabine refer to the study from Pittsburg, PA in which they used an animal model. I also printed out a list of side effects and dosage regiment. I did print out a few of the things that @benryu posted on proof that the Potassium channels earlier in this thread. I wish you the best of luck on getting the Retigabine but feel like your Psychiatrist might be hesitant to prescribe it if he or she doesn't know the drug.
Best of luck and hope this helps. I wish I had the links but I looked up so many articles and I'm not sure which ones I printed.

 

[Dedas]

It would be very useful to collect all links in a post so that people have something to show their doctor.

 

[benryu]

Hi @cdog ,

Thanks for your comment, it's pretty late here in montreal, so I'll be short
(EDIT: I wanted to be short, but I could not resist writing a lot lol, I am such a failure haha)

I think I already covered this question a few weeks ago, maybe this is what you're looking for:
If not we can obviously discuss more in a dedicated thread or in the private chat.

http://etd.fcla.edu/CF/CFE0001911/Soundarapandian_Mangala-Meenakshi_200712_PhD.PDF.pdf
Start reading page 3, it's not in your exact terms, but if you read it to the end, this is it. It describes the mecanism of interaction between glutamate
I picked this article because I though it was simple enough for non technical.

This is the hardcore version, it's more specific but far more complex to read:
http://www.pnas.org/content/109/21/8292.full.pdf#page=1&view=FitH

And I found this summary that is easy to understand, you can go for that, I am sure it will make you happy!
http://www2.le.ac.uk/departments/cpp/staff/dr-martine-hamann/hamann-neuroscience-group
(This is from the head of reasearch on the AUT00063 project.)

I'll make an additional comment on the action potential:
Basically when you touch your hand you feel it, the nerve is transmiting an electrical message through the spine to your brain.

This is basically the action potential, so when you hear a sound, the information is transmited to your brain in a similar fashion.

Imagine each cell (axone) is closed by a membrane (voltage gated channels):

Outside you have sodium, inside you have potassium, it's a resting state.


When you have a stimuli, sodium goes in through the sodium gate and it changes the sign, it's the depolarization

Then potassium gate open to let potassium out and change the sign again it's the repolarization


Then the sodium potassium pump evacuate the remaining sodium and the cell becomes ready for another cycle


The entire cycle looks like this:



Now what happens when you have T., the potassium voltage gates don't work very well, and don't let the potassium go out correctly, it means the sign never totally change and a continuous signal is transmited to the brain, in other word Tinnitus.

If you look at the document from dr hamann:
http://www2.le.ac.uk/departments/cpp/staff/dr-martine-hamann/hamann-neuroscience-group

This is what they are talking about, the signal become heratic, burst and shit and cannot go in rest mode.

All of this because of a defficient potassium channel: Kv3.1.

The glutamate create what we call otoxicity and this phenomenon affect the potassium channels, it's locked by platicity in a very short time (days, maybe weeks).
They proved that on chicken
http://www.nrronline.org/article.as...olume=7;issue=9;spage=714;epage=718;aulast=Yu

If a drug comes and forces the specific potassium channels to act normally, plasticity will lock in the other way and those axone will be able to go in rest mode, in other words, let you experience silence again.

Hope this help !
Now I go to bed, it's 3am and I give class tomorrow morning haha ^_^