Flupirtine — Another Potassium Channel Opener

[lapidus]

I have contacted @attheedgeofscience and he has informed me that he has resumed his experiment with Flupertine.

" I can - and will - try to go up to a daily dose of 600mg in a few days (I already started on the 400mg daily dose). "

Let's hope for good results. If I get any updates from him in the future I will update this thread.

That's odd. @FERNANDO GIL has also had contact with ATTEOS and apparently ATTEOS' T is 70% lower now because of LLT. Why will he start this stuff in the middle of his LLT healing? How does he know that his 70% lowering is from LLT and not from this stuff then?

And yes loco, keep in touch with him and report back to us

 

[attheedgeofscience]

Update... I have been on 400mg dose for 4 days now. I have timed the increase to 600mg to coincide with the first day of the weekend (ie. tomorrow). I am not too sure of Flupirtine's therapeutic potential as a "tinnitus combatant" - the drug has been around for quite some time now, and the first studies - in relation to tinnitus - were done already more than 10 years ago. However... more than anything is the importance of dosage rather than duration of treatment. So unless I have actually tried the daily 600mg daily dosage, I will never know the drug's actual potential.

I did track down a 2006-paper on a treatment protocol trial for Flupirtine in relation to tinnitus - and carried out by none other than the well-known (tinnitus) neurosurgeon, Dirk De Ridder:

http://www.ncbi.nlm.nih.gov/pubmed/17114151

However, as can be seen, the study only used a maximum daily dosage of 200mg Flupirtine (in all cases). The study should - as a minimum - have put the various groups of patients on daily dosage of 200mg, 400mg, and 600mg, respectively. With just one group of volunteers using a daily dosage of 200mg, they might as well not have done the experiment in the first place; seems like one of those LLLT studies designed-to-fail, in my opinion. Problem is... this study was done - in part - by Dirk De Ridder, and that causes me a "headache"...

Flupirtine is kind of a special drug - it is a fairly strong analgesic, but it neither belongs to the opioid- nor the NSAID-group. It is a unique painkilller (and muscle relaxant). It is generally well tolerated - except for one specific side effect: liver toxicity.

 

[SoulStation]

Good luck with this. Thanks for the update.

 

[Juan Carlos]

Any update? after reading the experience from Christian78, its worth considering other drugs with less side effects than retigabine

 

[tomm]

How do you feel after 2 weeks @attheedgeofscience ? Noticed any improvement?

 

[attheedgeofscience]

I am going to wait a little before doing a proper update. There has been a lot of information to take in due to my consultation with Prof. Jeanmonod in Switzerland.

I seem to have seen some improvements, but the improvements do not appear to be directly correlated with the medication being present in my blood. A recent paper on the pharmacology of potassium channel openers - http://www.ncbi.nlm.nih.gov/pubmed/24681057 - reveals that this class of CNS medication does have theoretical potential when it comes to treating tinnitus, but that dosage is somewhat important. In this respect, Trobalt has a better treatment potential than Flupirtine. But Flupirtine has a better overall safety profile than Trobalt (except for liver toxicity). It is easier to achieve a therapeutic effect with Trobalt (against tinnitus). To achieve a similar therapeutic effect with Flupirtine, I estimate "informally" that I would need to exceed the maximum daily allowed dosage of 600mg. I need to decide whether it would make sense to do a quick increase to 700 or 800mg for a couple of days.

The aim is to observe a decrease in tinnitus while being on the medication (so that I know where the decrease in my tinnitus is coming from).

The more I read about Flupirtine, the more interesting this unique drug appears to be. It is currently (also) being investigated as a potential treatment option for other neurological diseases such as MS, Creutzfeldt-Jakob's disease, and ALZ.

 

[attheedgeofscience]

Besides @Denny who does not appear to be signing in on the forum anymore, does anyone know if this board has a pharmacist on it? By "pharmacist", I mean someone with a MSc degree in pharmacology (not a pharmacist assistant).

Thanks.

 

[Juan Carlos]

I was getting informed about Flupirtine and found this document, that says the followring

Against the background of a steadily increasing patient exposure Germany has observed a growing number of reports of probably idiosyncratic liver toxicity associated with flupirtine. Reactions ranged from asymptomatic liver enzyme elevation to fatal liver failure or liver transplantation.
The German database of adverse drug reactions has recorded a total of 954 reports for flupirtine including 330 reports from the SOC hepatic and biliary disorders. 49 cases from this SOC reported liver failure and 15 cases had a fatal outcome or resulted in liver transplantation.

So, even it has less "number of side effects" than Retigabine, the liver toxicity its a very serious thing. Even in the case it works better for Tinnitus, wich is not proved and everyday we have more evidence than Retigabine kills T, I wouldn't give a try, "liver" is the most important organ to "live"

Liver enzyme elevations were noted in 31 % of patients receiving flupirtine for ≥ 6 weeks.
Germany has received several reports of severe liver toxicity including cases with a fatal outcome or leading to liver transplantation. Causality has been assessed as at least possible in part of these cases. Additional cases have been described in the literature. The majority of these cases seem to occur after a treatment duration of several weeks. While no cases of severe liver toxicity were observed in published clinical trials liver enzyme elevations in up to 58,6 % of patients were noted.

It hasn't been tester for long periods of time, they always speak about Weeks, while Retigabine has been tested up to 4 years on maximum dose (yes, also with some bad side effects in some cases of very long term intake, wich is not necessary for tinnitus aparently)

 

[attheedgeofscience]

I was getting informed about Flupirtine and found this document, that says the followring
So, even it has less "number of side effects" than Retigabine, the liver toxicity its a very serious thing. Even in the case it works better for Tinnitus, wich is not proved and everyday we have more evidence than Retigabine kills T, I wouldn't give a try, "liver" is the most important organ to "live"

It hasn't been tester for long periods of time, they always speak about Weeks, while Retigabine has been tested up to 4 years on maximum dose (yes, also with some bad side effects in some cases of very long term intake, wich is not necessary for tinnitus aparently)

...Agreed - and that's why you will have seen me mention "hepatotoxicity" in just about all of my posts!

 

[Juan Carlos]

...Agreed - and that's why you will have seen me mention "hepatoxicity" in just about all of my posts!

yes, i read it of course, that's why i wanted to check how serious is that toxicity and now i see is quite serious

My opinion: In the case this was the last resort in the world about Tinnitus and had very severe one, i would give a try. But having some alternatives, for example retigabine wich is really working, or in some future time Autifony, or for some people now Tibetan herbs agar35, i think it doesn't worth to try and risk a healthy liver wich could be a very big problem, much more serious than T from a health viewpoint.

 

[attheedgeofscience]

"Mini"-update...

I took my 2nd 400mg Flupirtine slow-release tablet yesterday evening before bedtime (knocks you off to sleep and helps reduce the feeling of sluggishness that a person would experience one or two hours after intake during daytime hours).

This morning, like yesterday morning, I definitely woke up with just about no tinnitus on the right side (= morse-code + low volume pulsatile/rythmic high pitched but unmaskable sound). My left-side tinnitus is a pure tone EEEEEEEEEEE-sound - and that sound is still present at the moment. Not much reduction, if any, I would say. This is probably why I haven't really felt an improvement in my own subjective terms earlier on, because my left-side tinnitus is the tinnitus that I developed most recently (and which therefore has my mind focused on it non-stop).

I will be taking two 100mg pills today in order to increase the daily dosage to 600mg (today). Tomorrow, I will decide whether to go to 700mg or not. There is no tappering requirement involved with Flupirtine (which is one of the topics I'd like to ask a pharmacist about - ie. if Trobalt and Flupirtine have similar CNS impact on Kv7.x channels, then why is there a taper required for one - and not for the other; is it due to the patient profile and not the drug itself ie. epileptics vs non-epileptics, for instance...?).

 

[Viking]

During the year 2008 i tried Efiret for max 4 weeks (flupirtina) under De Ridder advice without significant results. Trobalt work better than Efiret but unfortunally i can't take it for more than 2 weeks before start to have kidney problems

 

[Juan Carlos]

During the year 2008 i tried Efiret for max 4 weeks (flupirtina) under De Ridder advice without significant results. Trobalt work better than Efiret but unfortunally i can't take it for more than 2 weeks before start to have kidney problems

hey, where that kidney problems attached to Trobalt? I dont remember to read it as a side effect. Did u had kidney problems before taking Trobalt?

 

[Viking]

hey, where that kidney problems attached to Trobalt? I dont remember to read it as a side effect. Did u had kidney problems before taking Trobalt?

No. I never had kidney problems. I made two attempts with Trobalt. the first time in about a week I had the problem of painful urination and a slight pain in his right side. with echo Doppler examination showed small calcifications renal then suspended the Trobalt and I solved by drinking lots of water and eating without salt. After about a month I started the Trobalt and after 10 days, at a dose of 100x3 day, I started to have a problem of incomplete emptying of the bladder. then again I had frequent urination and slowly perineal pain in the stretch. I had to pause it but looked very effective, even though I was pretty drunk.

 

[Christian78]

you maybe need to ease with milk and a oxalates like black tea, as stones are Calcium oxalate, more magnesium to bind calcium.... maybe i say ...

And urination well, did you sit to pee or sit to pee? sit is natural position. i wonder why not lower dosage like 250...

 

[Viking]

you maybe need to ease with milk and a oxalates like black tea, as stones are Calcium oxalate, more magnesium to bind calcium.... maybe i say ...

And urination well, did you sit to pee or sit to pee? sit is natural position. i wonder why not lower dosage like 250...

Not sit. If i sit is more bad. 250mg is too low dosage to be an effective treatment. Minimum efficacy start with 100x3. Better was 100 + 200 + 100 + Clonazepam.
I have read this: http://www.vertigo-dizziness.com/english/tinnitus/is-it-possible-a-recovery-from-tinnitus.html

i'm very courius what mix of drugs used to treat it? Their statistics are staggering!
Showed 61% to full restitution of tinnitus
30% an important decrease of the symptom Which Allows People to follow a normal lifestyle.
9% of cases do not show any improvement in symptoms or Reasons on Which consultation was originated....

 

[Carlos1]

Not sit. If i sit is more bad. 250mg is too low dosage to be an effective treatment. Minimum efficacy start with 100x3. Better was 100 + 200 + 100 + Clonazepam.
I have read this: http://www.vertigo-dizziness.com/english/tinnitus/is-it-possible-a-recovery-from-tinnitus.html

i'm very courius what mix of drugs used to treat it? Their statistics are staggering!
Showed 61% to full restitution of tinnitus
30% an important decrease of the symptom Which Allows People to follow a normal lifestyle.
9% of cases do not show any improvement in symptoms or Reasons on Which consultation was originated....

Viking that's a very interesting article ...how can we find more about that type of treatment ?

 

[Viking]

Viking that's a very interesting article ...how can we find more about that type of treatment ?

I'm searching on pubmed by name of authors but i don't find more. Tomorrow i will call

 

[SethL]

@Viking
Were you able to get through to anyone from the article above? I read through it and looked at their presentation slides as well. They definitely promote utilizing more than one drug to treat T.

 

[tomm]

How are you getting on with the flupirtine @attheedgeofscience ?

Any difference on the left side pure tone?

 

[attheedgeofscience]

UPDATE

The concept of the heterogeneity of tinnitus is uncommon knowledge amongst medical professionals, but well known amongst researchers of tinnitus. I have since the beginning of my ordeal assumed (= "known") that there is likely to be both a cochlear and a neurological component to tinnitus. It is for that reason that I did both two stem cell treatments and cold laser therapy in order to target the cochlea and the repair, thereof. I also focused on the neurological aspect of tinnitus by visiting the Swiss neurosurgeon, professor Jeanmonod, as well as looking into a possible pharmaceutical treatment (Flupirtine).

I am not sure where to "place" this update as I have been doing both LLLT and Flupirtine during the past 8 months. At this point I seem to have entered a new stage of progress. I am having days such as today where my right side (and life-long) tinnitus is 100% gone. In the past, I would generally notice my left side tonal eeeeee-tinnitus more whenever my right side tinnitus would be gone (or nearly gone). However, this has now changed (at least on some days). Today, for instance, my improvement is approximately R/L = 100%/75% (and I am even having brief periods of 5 to 10 minutes where it is about R/L = 100%/90%).

I have decided to do another round of Flupirtine to try to "cement" the improvement so that my tinnitus level does not fluctuate from day-to-day (i.e. yesterday it was about R/L = 50%/50% which is what I consider to be my baseline improvement i.e. it never gets worse than this). Flupirtine is quite an interesting drug and chemically similar to Trobalt. Its pharmacological profile along with similarities/differences in relation to the suppression of tinnitus can be found in literature such as:

http://digital.library.unt.edu/ark:/67531/metadc287994/m1/1/

The treatment of tinnitus is - for the reasons mentioned above - likely to require a multi-faceted approach (which is also exactly what I have done). With more than one variable at play, it is - however - difficult for me to pinpoint where my improvement has come from - but "something" is happening. On days such as this one, I can definitely feel my energy-levels picking-up; it's like being born again. Or almost!

I will see how I get on in the coming week; Flupirtine does not require tapering (unlike Trobalt), but treatment cycles should be kept short due to liver toxicity (which may develop rather suddenly). I will consider seeing a neurologist here in Germany in relation to a prescription of Trobalt (depending on how I get on in the coming week). On days like this, I sense that "victory" may be near.

attheedgeofscience
19/FEB/2015.


Relevant links/sources

Research papers on inner ear hair cell repair using cold laser:

http://synapse.koreamed.org/DOIx.php?id=10.3342/kjorl-hns.2009.52.1.19&vmode=PUBREADER
www.ncbi.nlm.nih.gov/pubmed/24343446


Clinical trial examining the use of stem cells for restoring auditory function in children:

https://www.clinicaltrials.gov/ct2/show/NCT02038972?term=hearing+loss+cord+blood&rank=2


"Justification" of a cochlear component to tinnitus (from the Auris Medical Q&A):

A: So far, AM-101 has been tested only in the acute stage, which according to some guidelines extends up to 3 months from onset. There is a certain consensus among experts that inner ear (peripheral) tinnitus may become centralized in some patients after the acute stage, which means that the target for a treatment may shift from the inner ear to the brain. However, the exact mechanism and timing of such centralization is unclear, and it must be noted that a considerable number of tinnitus sufferers will probably never experience any centralization at all. In the absence of reliable diagnostics to distinguish between peripheral and central tinnitus, we consider it prudent to explore AM-101's time window with a step-by-step approach. First, we need to demonstrate that AM-101 works in the acute stage and get it approved – in a second step, we will expand on this and seek to find out how far we can go. This is reflected by the design of our European trial, where we are testing AM-101 primarily in the acute setting, but in a separate stratum also in the post-acute setting (up to 12 months from onset).

A: We are currently testing AM-101 for its effects on tinnitus caused by acute acoustic trauma, barotrauma (excessive pressure changes from flying or diving), surgery related trauma or otitis media. We started our research with AM-101 in tinnitus triggered by acute acoustic trauma – here you can understand fairly well what is going on in the cochlea following a brief, heavy bout of noise exposure, and an animal model could be developed. For our first clinical trial in humans, we remained close to that model by recruiting soldiers suffering from tinnitus after acute acoustic trauma. In further clinical trials we expanded the criteria to include also barotrauma, surgery trauma and otitis media as onset factors – because the same mechanisms are at work as in acute noise trauma. There is an excessive release of glutamate, which in turn triggers so-called glutamate excitotoxicity – there is damage to sensory cells in the cochlea similar to what happens in stroke. There are various other types of traumatic or non-traumatic injuries to the cochlea where glutamate excitotoxicity is known or suspected to be involved. We therefore expect that AM-101 could work also in other types of tinnitus; but this remains to be confirmed by further testing.

Literature documenting the specific pathological processes that occur in the cochlea (along with the unique repair mechanism that takes place following inner ear hair cell death; this includes the notion of scar tissue - a topic I commented on before in a few of my posts):

http://bmb.oxfordjournals.org/content/63/1/25.full

 

[marqualler]

Thanks for the update @attheedgeofscience -- this sounds fantastic. Would you mind sharing what your LLLT dosages and Flupertine dosages have been?

 

[locoyeti]

UPDATE

The concept of the heterogeneity of tinnitus is uncommon knowledge amongst medical professionals, but well known amongst researchers of tinnitus. I have since the beginning of my ordeal assumed (= "known") that there is likely to be both a cochlear and a neurological component to tinnitus. It is for that reason that I did both two stem cell treatments and cold laser therapy in order to target the cochlea and the repair, thereof. I also focused on the neurological aspect of tinnitus by visiting the Swiss neurosurgeon, professor Jeanmonod, as well as looking into a possible pharmaceutical treatment (Flupirtine).

I am not sure where to "place" this update as I have been doing both LLLT and Flupirtine during the past 8 months. At this point I seem to have entered a new stage of progress. I am having days such as today where my right side (and life-long) tinnitus is 100% gone. In the past, I would generally notice my left side tonal eeeeee-tinnitus more whenever my right side tinnitus would be gone (or nearly gone). However, this has now changed (at least on some days). Today, for instance, my improvement is approximately R/L = 100%/75% (and I am even having brief periods of 5 to 10 minutes where it is about R/L = 100%/90%).

I have decided to do another round of Flupirtine to try to "cement" the improvement so that my tinnitus level does not fluctuate from day-to-day (i.e. yesterday it was about R/L = 50%/50% which is what I consider to be my baseline improvement i.e. it never gets worse than this). Flupirtine is quite an interesting drug and chemically similar to Trobalt. Its pharmacological profile along with similarities/differences in relation to the suppression of tinnitus can be found in literature such as:

http://digital.library.unt.edu/ark:/67531/metadc287994/m1/1/

The treatment of tinnitus is - for the reasons mentioned above - likely to require a multi-faceted approach (which is also exactly what I have done). With more than one variable at play, it is - however - difficult for me to pinpoint where my improvement has come from - but "something" is happening. On days such as this one, I can definitely feel my energy-levels picking-up; it's like being born again. Or almost!

I will see how I get on in the coming week; Flupirtine does not require tappering (unlike Trobalt), but treatment cycles should be kept short due to liver toxicity (which may develop rather suddenly). I will consider seeing a neurologist here in Germany in relation to a prescription of Trobalt (depending on how I get on in the coming week). On days like this, I sense that "victory" may be near.

attheedgeofscience
19/FEB/2015.


Relevant links/sources

Research paper on inner ear hair cell repair with cold laser:

http://synapse.koreamed.org/DOIx.php?id=10.3342/kjorl-hns.2009.52.1.19&vmode=PUBREADER


"Justification" of a cochlear component to tinnitus (from the Auris Medical Q&A):





Literature documenting the specific pathological processes that occur in the cochlea (along with the unique repair mechanism that takes place following inner ear hair cell death; this includes the notion of scar tissue - a topic I commented on before in a few of my posts):

http://bmb.oxfordjournals.org/content/63/1/25.full

that is great news @ateos. i don't like to push solutions onto others because there is so much we don't know and there is a lot of uncertainty, but given that there are no real treatments for tinnitus and the positive (non-placebo) results from RTG i think it's clear that Kv7 modulators are the way to go. i really hope more people try RTG or Flupertine so we can get some more data. i look forward to your updates.

 

[lapidus]

@locoyeti

And Keppra

 

[locoyeti]

@locoyeti

And Keppra

i haven't looked into Kv3 yet, but if i'm not mistaken keppra is a Kv3 modulator. i think the jury is still out on those, i think only one person said he had improvement on keppra. i hope Kv3 modulators eventually work out (aut0063), but i think there is a big distinction between Kv7 and Kv3, and there is much more info on Kv7 at this point in time. at some point i would like to dive into the Kv3 literature though, its just that i have seen so much improvement from the Kv7.

 

[lapidus]

i haven't looked into Kv3 yet, but if i'm not mistaken keppra is a Kv3 modulator. i think the jury is still out on those, i think only one person said he had improvement on keppra. i hope Kv3 modulators eventually work out (aut0063), but i think there is a big distinction between Kv7 and Kv3, and there is much more info on Kv7 at this point in time. at some point i would like to dive into the Kv3 literature though, its just that i have seen so much improvement from the Kv7.

It's only @Viking so far who have tested Keppra and it didnt have any effect on his T but his H vanished. Other than that you're right, kv3 seems to be undiscovered territory but hopefully Autifony knows what they're doing.

 

[Philip83]

Thanks for the update @attheedgeofscience -- this sounds fantastic. Would you mind sharing what your LLLT dosages and Flupertine dosages have been?

I second this. What LLLT -clinic did you visit and what were the specs/duration (nr of sessions and per session) of the treatment? I'm currently looking into maybe trying this. Thanks!

 

[Zimichael]

i haven't looked into Kv3 yet, but if i'm not mistaken keppra is a Kv3 modulator. i think the jury is still out on those, i think only one person said he had improvement on keppra. i hope Kv3 modulators eventually work out (aut0063), but i think there is a big distinction between Kv7 and Kv3, and there is much more info on Kv7 at this point in time. at some point i would like to dive into the Kv3 literature though, its just that i have seen so much improvement from the Kv7.

Loco...Before you dive into Keppra be sure to check back on the thread as I covered a fair amount of ground there trying to figure out just what it "was/is"...Kind of hard to be sure actually as sources gave different answers.
However I agree that there is scads more info on the Kv7's than the Kv3's for some reason. The difference in published articles/info./volume between the two classes is huge.
Pity, seeing as AUT00063 is Kv3.

Best, Zimichael

 

[attheedgeofscience]

UPDATE

Since my last update, I have been taking 400mg Flupirtine in the slow release tablet form. I take it just before bedtime as I might as well benefit from the sedation effect it has (Flupirtine is an analgesic/muscle relaxant) - however, I don't have problems to get to sleep otherwise (in general I take no medication for sleeping).

As I have previously experienced when taking Flupirtine, my right side tinnitus is pretty much eliminated; this would also happen from time-to-time even without being on Flupirtine as my right side tinnitus tends to have a cyclic pattern to it with a cycle of about 3 to 4 days. However, the last four days have been totally steady (right side) with an improvement of about 85% to 100%. So there is no doubt that Flupirtine does "something".

This morning, I woke up with a distinctly low left side tinnitus, as well. In fact, the first 10 minutes, I was essentially cured. It has started to pick-up just a tiny bit, but my left side tinnitus is no longer the usual tonal eeeeee-sound (more like a soft "electric hum", if that makes sense...).

It is by no means time to open the champagne bottles just yet; I am simply reporting what I experience, as I experience it...

Side-effects? Well, Flupirtine is very well tolerated by myself. I don't get anything close the side effects I have read about in the accounts in the main Trobalt-thread (and Flupirtine does act on the same channels as Trobalt). The only side-effects I experience is a mild sluggish feeling, slight cognitive impairment, and I notice I tend to write words that shouldn't be there or that make no sense. For example, in the sentence above, "This morning, I woke up with...", I initially wrote "This morning, I would up with..."; also my spelling is not as good as it would be when not taking Flupirtine.

 

[Mo_Mo]

@attheedgeofscience many thanks for the update, are you also still doing LLT? Or have you stopped LLT? Also in the past 8 months what has been you cycle of using flupirtine are you using it for a week each month? Also sometimes with trobalt users they experience spikes then a reduction, you had mentioned that you got a beep that was different than T similar to the one you got when you did stem cell, was this a one time experience or do you go get this beep from time to time with flupirtine