Retigabine (Trobalt, Potiga) — General Discussion

[Grace]

@Telis , if i remember you couldnt get this cause your in canada?

 

[dan]

Only if someone is interested. These are the countries where Trobalt is available in Europe:

"The medicine is available as tablets in the following Member States: Austria, Belgium, Bulgaria, the Czech Republic, Denmark, Estonia, Finland, France, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom."

Source: http://www.ema.europa.eu/ema/index....news_detail_001802.jsp&mid=WC0b01ac058004d5c1

We have a member in Iceland who cannot get his hands on Trobalt (?)
That list is inconclusive.

 

[bedouin]

UK Peeps, please keep us updated re drug accessibility. Cheers!

I'm on the AM101 trial but no movement in my T since 1st set of injections (19th - 21st Aug). It's the TACTT3 so placebo or real drug so no one knows. Will apply for Autifony when it opens but doubt i will be able to participate due to being on AM101. Retigabine would DQ me from AM101 so i would only be able to see if i can get it, not take it, if i went to a doctor. But i will try all the same.

 

[rtwombly]

my mother would say even 1000% transformation.

That is who we want to be happy, so congratulations!

@Christian78 Do you feel it will not benefit you to increase dosage again or are you still upping dosage slowly?

 

[Christian78]

Well i dont think i will go up in dosage, not for now.

 

[locoyeti]

@Markku how do we access the information on the forms?

I hope that the formality of filling out forms, however simple the form, doesn't dissuade a participant who would rather just casually update us with a post. I know I am lazy enough to when it comes to filling out forms. We should probably make it as easy as possible for participants to give us updates, and emphasize that the forms are optional.

 

[Markku]

@Markku how do we access the information on the forms?

I hope that the formality of filling out forms, however simple the form, doesn't dissuade a participant who would rather just casually update us with a post. I know I am lazy enough to when it comes to filling out forms. We should probably make it as easy as possible for participants to give us updates, and emphasize that the forms are optional.

You can't, it's something that we need to put together and post as a separate post. We'll do it every once in a while, whenever there's a meaningful amount of data gathered. We'll see how it goes.

I think your worry may be unfounded, all those people who've completed the form have also written updates in this thread. And if there will be people who don't write in the thread, but fill out the forms, we'll make sure the data is published properly --- well, like it will be anyway.

 

[Markku]

We have a member in Iceland who cannot get his hands on Trobalt (?)
That list is inconclusive.

Hmm, that list is from May 2013 taken from the news piece about restricting Retigabine to last-line treatment of partial epilepsy...

So maybe Icelandic doctors are just as wary about prescribing it off label as Finnish doctors. I know there is *one* doctor specialized in tinnitus in Finland (5.4M people) who might, and just might consider prescribing Trobalt for the most extreme tinnitus case. Plus Iceland is tiny in comparison and, as far as I know, they tend to be pretty strict about off label prescriptions similar to how it is here.

I suppose it was @RaZaH who tried getting his hands on it? May I ask @RaZaH did you see more than one doctor? Did he or she say it's not available in the whole of Iceland? Or just that it's not prescribed off label for tinnitus? Wonder if it's the same there as here...

 

[RaZaH]

The drug is available in Iceland, in one drugstore, prescribed to one patient in the whole country.
I am getting closer to obtaining it ...I hope, seems everytime I get close something else comes up.
I might get Trobalt tomorrow if everything works out.
Wish me luck.

(only been to one doctor as of yet)

 

[cdog]

Don't know if this was posted, but I found this to be very informative:
http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2009.00111.x/full

One interesting section from the article :

How does stimulating mAChRs close M-channels?
It has been clear for some time that M-channel inhibition is a rather indirect response to mAChR stimulation (Figure 2), and that it was likely to be associated with the well-known effect of Gq activation, to stimulate phospholipase Cβ and catalyse the hydrolysis of membrane phosphatidylinositol-4,5-bisphosphate (PIP2) (Marrion, 1997). Earlier work concentrated (not surprisingly) on the actions of the products of this hydrolysis, inositol-1,4,5-trisphosphate (IP3) and diacylglycerol as potential 'diffusible messengers'. However, the more recent demonstration that – like many other membrane proteins – Kv7 (and native M) channels actually required PIP2 in order to enter the open state and close when membrane PIP2 levels are reduced or its polar head groups neutralized (Suh and Hille, 2002; Zhang et al., 2003; Robbins et al., 2006; Suh et al., 2006) has led to a complete volte-face – namely, that closure results, not from the accumulation of hydrolysis products but instead from the reduction in membrane PIP2 levels that results from its hydrolysis. Perhaps the most convincing evidence for this is that mAChR-induced inhibition of both expressed Kv7.2/7.3 channels and native neuronal M-channels is actually reduced or prevented when membrane PIP2 levels are increased by over-expressing the PI5-kinase (Winks et al., 2005; Suh et al., 2006), rather than increased as would be anticipated were closure to depend on hydrolysis products. This in turn has highlighted the very large and rapid changes in membrane PIP2 levels following mAChR stimulation, the concentration apparently falling by 90% plus within a few seconds (Winks et al., 2005; Suh et al., 2004; see also Willars et al., 1998). Direct evidence for this rapid depletion has recently been obtained by using a fluorescent probe that binds to PIP2 in the membrane then moves into the cytosol as PIP2 levels fall (Hughes et al., 2007; Quinn et al., 2008). The primary PIP2-binding site in the Kv7.2/7.3 channel has recently been identified as a cluster of basic amino acids in the carboxy-terminus (Hernandez et al., 2008): homology screening suggests that this region forms an interaction site with membrane lipids similar to that formed by Kir channels, which are also activated by PIP2 (see Logothetis et al., 2007).

To summarize (according to how I understood it) - the molecular mechanism of why Kv7 channels close in the first place, is thought to be caused to the decreased levels of the PIP2 (a phospholipid component of the membrane). When they increased those levels by over-expressing PI5-kinase (an enzyme), the Kv channel inhibition was reduced or prevented. (see bolded text above).

If so, can something (a drug, etc.) that overexpresses PI5-kinase help open up the Kv7 channels? Could this be another approach?

 

[rtwombly]

To summarize (according to how I understood it) - the molecular mechanism of why Kv7 channels close in the first place, is thought to be caused to the decreased levels of the PIP2 (a phospholipid component of the membrane). When they increased those levels by over-expressing PI5-kinase (an enzyme), the Kv channel inhibition was reduced or prevented. (see bolded text above).

If so, can something (a drug, etc.) that overexpresses PI5-kinase help open up the Kv7 channels? Could this be another approach?

Doesn't appear to be selective enough. To be more effective and less side-effect prone than retigabine, the drug would have to target Kv7.4 exclusively (and maybe Kv7.1, though how it'd do that without affecting the heart is an open question). Opening Kv channels in general, or even just Kv7 channels would have effects we don't want. Now if there's an enzyme that acts only on Kv7.4, that's a path worth exploring.

 

[SoulStation]

Interesting clinical trial. Thank you for reporting it.

I just found this April, 2012, pdf on urinary retention and tinnitus--the actual numbers during the clinical trials. Everyone interested in the drug should read it. While rare (2%) and reversible, urinary retention is serious. Other kidney problems, notably Hydronephrosis, is also serious and occurred in two people participating in Retigabine's clinical trials.

https://www.gsksource.com/gskprm/en/US/images/gsk_content/POTIGA/PGA056R0_REMS_HCP_Letter_DC.pdf

http://en.wikipedia.org/wiki/Hydronephrosis​

Thank you I am utterly terrified now thanks to that wiki photo. Maybe it's a reality check I need.

 

[jazz]

I might get Trobalt tomorrow if everything works out.
Wish me luck.

Yes, be sure to let us know! Good luck!

 

[jeannie]

wow!!! great news please keep us informed... i may ask my doctor for this med...

 

[jeannie]

yes many people have gotten tinnitus from syringing ears....

 

[Eric Fridley]

I will be going to my gp next week to see if he will give me a prescription of this stuff I have had tinnitus for almost 3 month so I'm still In the acute stages idk how I got my T I had surgery and got my gall bladder removed took OxyContin for 3 days for the pain and on the third day I was just sitting watching tv around 12:00 pm I started to hear my left ear ring for no reason it sucks only my left ear rings and since it's been about 2 months and 27 days it's pretty much in my head now I have a thread if u want to read it i do have tmj will I think I do doc keep telling me a lot of people have clicking in there jaw and they just live with it so I have not got a MRI scan on my jaw yet thought it was my teeth so I got 3 wisdom teeth pulled 2 on left side and 1 on right had a dead tooth extracted also dentist told me it might be that but been a week and no deffrence in my tinnitus ummmm but yea if u want to hear my whole story u can Goto my thread but I will be getting this drug next Week should be easy since I live in the United States and I have access I'll keep u guys updated after I get it

 

[undecided]

There's a lot of talk about retigabine (a potassium opener) but very little has been mentioned about the other player in the tinnitus game.
There are a lot of sodium blockers (mostly anticonvulsants, like retigabine) which don't seem to get any love around here... Maybe someone has tried them? Like Lamictal or Topamax or whatever. Maybe in conjunction with retigabine?

 

[dan]

Sodium blockers won't cut it.

 

[Christian_B]

I consider more and more to ask my ENT for Trobalt. I'm just a little scared of the side-effects, i might wait for AUT00063, or the other drug like Trobalt, just without the side-effects.

Im actually doing OK during the day, but my nights keep to vary a lot. Sometimes i just can't sleep even im sick tired, and it feels like my brain just won't sleep because of the T, in the end i always fall asleep but it takes up to 2-3 hrs sometimes, and that's just not nice at all.

 

[Johno]

Report:

Hello . I was on 3x50 entry dosage from 26 august to 2 september.(From 3 september i am at 100mg dosage)

My report: 50mg dosage is nearly ineffective, except central T and hissing. Central T is quieter 30%-50% and hissing is still here, but it is more soft and less intrusive. Tonal side Tinnituses are without changes. Effects are most noticeable three hours after pill swallowing, after another 2 hours it slowly fades away.

I had one side effect - mild bladder pressure, feels like bladder cold, but for now its nearly disappeared - body needs some time to adapt retigabine chemistry. 50mg dosage is good for this adaption - possible side effects are much more tolerable (now with 2nd day with 100mg dosage, bladder issue is not worsening) . No problems with urinating.

I have only one pack of Trobalt, 84x100mg, i hope i will be able to get another(200mg), because doctor is on 3-week vacation from sept. (she had wedding last weekend).

If not, experiment will have to be interrupted.

 

[undecided]

Those are 168 doses @Johno at 50mg a pop.
You should be good for 168/3 = 56 days
Nice to read you have some positive results.

 

[SteveToHeal]

Report:

Hello . I was on 3x50 entry dosage from 26 august to 2 september.(From 3 september i am at 100mg dosage)

My report: 50mg dosage is nearly ineffective, except central T and hissing. Central T is quieter 30%-50% and hissing is still here, but it is more soft and less intrusive. Tonal side Tinnituses are without changes. Effects are most noticeable three hours after pill swallowing, after another 2 hours it slowly fades away.

I had one side effect - mild bladder pressure, feels like bladder cold, but for now its nearly disappeared - body needs some time to adapt retigabine chemistry. 50mg dosage is good for this adaption - possible side effects are much more tolerable (now with 2nd day with 100mg dosage, bladder issue is not worsening) . No problems with urinating.

I have only one pack of Trobalt, 84x100mg, i hope i will be able to get another(200mg), because doctor is on 3-week vacation from sept. (she had wedding last weekend).

If not, experiment will have to be interrupted.

Thanks Johno for the update. It sounds like something IS happening to your T and heading in the right direction. Good luck with getting a new supply of meds and staying on course getting the 200mg supply.

 

[Bogdan]

Retingabine works similar to gabapentin first on K Canals, the second one on Ca canals. So it works on neuropathic pain.

 

[Zimichael]

Ah, how long that is good question maybe 4-5 weeks on 200 mg.

Christian...sorry to be pedantic, (sort of like 'fussy') but when you post your dosages could you please clarify how many times a day as well as the mg... Like I am presuming you are taking 200 mg TID = 3 x a day = total of 600 mg per day.
Am I correct?

Also I would be interested to know if you are taking before meals/food, with meals/food, after meals/food...or on an"empty stomach".

And REALLY great that you have such an improvement overall as well as with the T...Super!

Best, Zimichael

 

[Zimichael]

I will be going to my gp next week to see if he will give me a prescription of this stuff I have had tinnitus for almost 3 month so I'm still In the acute stages idk how I got my T I had surgery and got my gall bladder removed took OxyContin for 3 days for the pain and on the third day I was just sitting watching tv around 12:00 pm I started to hear my left ear ring for no reason it sucks only my left ear rings and since it's been about 2 months and 27 days it's pretty much in my head now I have a thread if u want to read it i do have tmj will I think I do doc keep telling me a lot of people have clicking in there jaw and they just live with it so I have not got a MRI scan on my jaw yet thought it was my teeth so I got 3 wisdom teeth pulled 2 on left side and 1 on right had a dead tooth extracted also dentist told me it might be that but been a week and no deffrence in my tinnitus ummmm but yea if u want to hear my whole story u can Goto my thread but I will be getting this drug next Week should be easy since I live in the United States and I have access I'll keep u guys updated after I get it

Good luck...You may want to read my posts on all that way back in the thread. (Zimichael search should do it).
I can almost guarantee that your insurance will not cover it even with a "seizures" diagnosis from your doc...as the insurance Co. will want you to get a more "friendly" med.
So be prepared to pay the big $$$ in cash.

Best, Zimichael

 

[Zimichael]

(What the hell is a + Multi-quote????? Yeah, yeah, me and my "Quoting war").

Hey @SoulStation ...the "meteorited" kidney pic there was what I regard to be a pretty extreme example of 'overdose proportions'. In fact I have great wonder that the subject of such could have been alive with stuff pouring out of holes that big...Uh, maybe the specimen was from an autopsy. All you wanted to hear. Ha, ha...

But seriously, urinary retention should not be sniffed at:
"Urinary retention is the inability to empty the bladder completely. Urinary retention can be acute or chronic. Acute urinary retention happens suddenly and lasts only a short time. People with acute urinary retention cannot urinate at all, even though they have a full bladder. Acute urinary retention, a potentially life-threatening medical condition, requires immediate emergency treatment. Acute urinary retention can cause great discomfort or pain."

I had dinner with one of my doc friends last night and asked him what to do if it developed while I was on Potiga...His reply was "see your neighbour" (a specialist urologist). Also that there are drugs that relax the muscles involved, but without even looking I can guess they may affect the same K channels that are causing it...or at least add more complex "what the hell do we do now ring-around-the-roses" issues for the poor neurons up in brain-land dealing with all this.

In summary, going up slow in dosage is number one. (As mostly reported from our testers experience too).
Then stopping immediately if retention really gets going, rather than just some initial twinges of discomfort or slight slowing of urine stream, which could almost be expected.

As a total aside....DO WE HAVE ANY WOMEN INTENDING TO TRY RETIGABINE??? Is this just a guy thing going on here??? Would be nice to get a more balanced gender perspective as there may be subtle differences in reactions, etc., etc., etc.

Thanks... Zimichael

 

[william2]

I would like to wish good luck and health to all participants in this wonderful trial.
as I'm new here, could someone please tell me how many people are trialling Trobalt, how chronic and what's the general picture emerging (looks favorable from what I can see).

it would be nice to see 50 people trying it, how about recruiting from other forum boards or even this one?
i will try and help.

 

[jazz]

In summary, going up slow in dosage is number one. (As mostly reported from our testers experience too).
Then stopping immediately if retention really gets going, rather than just some initial twinges of discomfort or slight slowing of urine stream, which could almost be expected.

Going up slowly will definitely minimize side effects; I'm not sure about urinary retention, though. I believe that can occur at any time. But it is not common. That said, if it occurs, I would discontinue the drug.

About women trying the drug, I can't since I've had urinary retention. Are there other interested women following the thread, even if still undecided?

 

[SoulStation]

(What the hell is a + Multi-quote????? Yeah, yeah, me and my "Quoting war").

Hey @SoulStation ...the "meteorited" kidney pic there was what I regard to be a pretty extreme example of 'overdose proportions'. In fact I have great wonder that the subject of such could have been alive with stuff pouring out of holes that big...Uh, maybe the specimen was from an autopsy. All you wanted to hear. Ha, ha...

But seriously, urinary retention should not be sniffed at:
"Urinary retention is the inability to empty the bladder completely. Urinary retention can be acute or chronic. Acute urinary retention happens suddenly and lasts only a short time. People with acute urinary retention cannot urinate at all, even though they have a full bladder. Acute urinary retention, a potentially life-threatening medical condition, requires immediate emergency treatment. Acute urinary retention can cause great discomfort or pain."

I had dinner with one of my doc friends last night and asked him what to do if it developed while I was on Potiga...His reply was "see your neighbour" (a specialist urologist). Also that there are drugs that relax the muscles involved, but without even looking I can guess they may affect the same K channels that are causing it...or at least add more complex "what the hell do we do now ring-around-the-roses" issues for the poor neurons up in brain-land dealing with all this.

In summary, going up slow in dosage is number one. (As mostly reported from our testers experience too).
Then stopping immediately if retention really gets going, rather than just some initial twinges of discomfort or slight slowing of urine stream, which could almost be expected.

As a total aside....DO WE HAVE ANY WOMEN INTENDING TO TRY RETIGABINE??? Is this just a guy thing going on here??? Would be nice to get a more balanced gender perspective as there may be subtle differences in reactions, etc., etc., etc.

Thanks... Zimichael

Thanks for your response. This is definitely not acute UR . I can pee. I'd just say if i notice it my stream is at 85-90% power as opposed 100% percent. The effects certainly have not got any worse but if they don't subside I'm going to talk to my GP or talk to a neurologist who knows the med and my most likely will stop taking it daily .

 

[jazz]

The effects certainly have not got any worse but if they don't subside I'm going to talk to my GP or talk to a neurologist who knows the med and my most likely will stop taking it daily

That's a good plan! Let us know what you decide and what the doctors say.