Flupirtine — Another Potassium Channel Opener

[Matchbox]

You"can't be bothered" arguing with me yet you continue to engage with me . Mr. money-making big shot. If you would truly be unbothered you'd shut your mouth and get back to work then. You are 32 years old pretending to be an expert online. Reading forum posts on Tinnitus Talk does not count as expertise. I've argued with people before on this website but at least they came with some solid arguments. You still have not disproven anything I said.

I have no interest in engaging with you further because you have absolutely zero value to contribute to the discussion. If you want to respond to me because you have a fragile ego and want to have the last word, be my guest. But I'm not going to take anything you write seriously (and I hope no one else does as well) just because you claim to have a "background", whatever that means. Again, if you'd care about anyone's safety you would actually post some information then. But you are only interested in arguing for the sake of it.

I love how your solution is stonewalling. Lol. I have a few more credentials at hand that allow more resources than simply pouring through forum posts which are biased anyway (though I've looked at lots, they obviously aren't exactly credible, but many journals are too, even paid ones frankly). I'm just surviving, not making big money. I don't owe you any explanation, time or sources when I've done the work and don't have the time to, and you won't heed any caution whatsoever where it's warranted. I scaremonger because there's a legitimate lower risk option which is basically in the bag now for the patient.

If you had no interest you'd stop replying, so I guess I'm hitting some ego?

Maybe it'll work for you simply out of an unwavering placebo effect now that you've got a case of somethingtoproveitis.

All the best, don't get worse.

 

[Jerad]

@StoneInFocus, if I may ask, what does your tinnitus sound like? Is it electrical or what kind of tone(s)? Thanks for the help. Looking forward to seeing your report — we're rooting for you.

 

[StoneInFocus]

@StoneInFocus, if I may ask, what does your tinnitus sound like? Is it electrical or what kind of tone(s)? Thanks for the help. Looking forward to seeing your report — we're rooting for you.

Yes you may ask. At its worst it's basically a cacophony of:

- The baseline of:



- The synthline (is that even a word?) of the first few seconds of this song:



- Some sounds starting from around 1:45 from this "song":



Plus some other sounds like sizzling in a a frying pan, static noise and higher pitched tones. Sometimes I hear voices too, a bit like how it sounds in a restaurant or a bar but in a really distorted way, like if you'd listened to a really low quality recording of it.

So I hope Flupirtine might seriously bring down and even cure our tinnitus and hyperacusis. If that's not a possibility, I hope (and suspect) it will give use enough relief to live our lives at least somewhat normally until more and better treatments become available in the next couple of years.

Like I said I am pretty optimistic about the drug so far. I will give a detailed report I think Saturday or Sunday. The reason I am waiting is because I want to find out what the side effects are of taking Flupirtine for a a couple of consecutive days before being overly optimistic and maybe causing false hope.

I also want to say that, yes, generic Flupirtine from the brand VASFREE 100 is available to order online from certain vendors, both in the EU and the US. But if you want to try this drug in the near future, it's best to order it as soon as possible.

 

[Jerad]

Plus some other sounds like sizzling in a a frying pan, static noise and higher pitched tones. Sometimes I hear voices too, a bit like how it sounds in a restaurant or a bar but in a really distorted way, like if you'd listened to a really low quality recording of it.

So I hope Flupirtine might seriously bring down and even cure our tinnitus and hyperacusis. If that's not a possibility, I hope (and suspect) it will give use enough relief to live our lives at least somewhat normally until more and better treatments become available in the next couple of years.

Like I said I am pretty optimistic about the drug so far. I will give a detailed report I think Saturday or Sunday. The reason I am waiting is because I want to find out what the side effects are of taking Flupirtine for a a couple of consecutive days before being overly optimistic and maybe causing false hope.

I also want to say that, yes, generic Flupirtine from the brand VASFREE 100 is available to order online from certain vendors, both in the EU and the US. But if you want to try this drug in the near future, it's best to order it as soon as possible.

Thanks for the help and info. Sounds like a lot and my tinnitus is a lot, too. It's electrical and sizzling; static; humming; drilling. I'm hoping Flupirtine is a good solution. I'm still in the acute stage technically, so maybe it could help reverse some of it?

 

[Travis Henry]

So who here has taken Flupirtine and had it lower their tinnitus and hyperacusis?

 

[DebInAustralia]

Honestly the liver damage potential just makes this a non starter especially with Xenon on the horizon.

Flupirtine opens Kv7.2 which doesn't seem to do much for tinnitus. Barely touched Kv7.1 which Trobalt did and is what Xenon is working on making safer, currently in Phase 2b I believe. The original formula will also be out in a different form for infants with seizures that don't primarily respond to GABA drugs.

I thought Kv 7.2/3 channels are specific to tinnitus?

 

[Jerad]

So who here has taken Flupirtine and had it lower their tinnitus and hyperacusis?

@undecided, @1MW and @attheedgeofscience reported positive results for tinnitus.

 

[Hottopic29]

You"can't be bothered" arguing with me yet you continue to engage with me . Mr. money-making big shot. If you would truly be unbothered you'd shut your mouth and get back to work then. You are 32 years old pretending to be an expert online. Reading forum posts on Tinnitus Talk does not count as expertise. I've argued with people before on this website but at least they came with some solid arguments. You still have not disproven anything I said.

I have no interest in engaging with you further because you have absolutely zero value to contribute to the discussion. If you want to respond to me because you have a fragile ego and want to have the last word, be my guest. But I'm not going to take anything you write seriously (and I hope no one else does as well) just because you claim to have a "background", whatever that means. Again, if you'd care about anyone's safety you would actually post some information then. But you are only interested in arguing for the sake of it.

Just take the meds. Let us know how it goes and how it benefits you. I hope it helps you

 

[StoneInFocus]

UPDATE:

The thing which I feared the most that would happen, already happened.

Before I started the treatment I was already worried about how taking a drug which has "NMDA receptor antagonist and GABAA receptor modulatory properties" for a couple of months would affect my mental health.

I will give a more elaborate experience report Saturday or Sunday, but for now I will discuss what happened yesterday.

Recap: I have taken 200 mg on Tuesday and 400 mg on Wednesday, both all the pills at once.

Thursday I had taken 100 mg around noon, and 300 mg around the late afternoon. Everything was going fine until around 23:00. I started ruminating more and more, especially about my tinnitus and hyperacusis. Just worrying about the same things over and over again. I took a shower, and when I emerged from it my tinnitus was very loud. I felt physical sensations of anxiety about it, which normally I don't do. I tried to sleep, but just when I was about to fall asleep, I thought about my tinnitus and hyperacusis again, which immediately sparked feelings of anxiety all throughout my body, especially around the stomach area. I eventually managed to fall asleep, but I distinctly remember how I was afraid I fucked up my mind again.

Now, this might not sound too serious but keep in mind I haven't felt like this for maybe half a year yet. If this is how I am going to feel every night (and maybe even worse) I am not going to take this drug anymore. I am afraid if I continue to take this drug in this particular fashion I will completely destabilize my mind. I think the GABAA modulation property is the bad guy here. Today I will not take any Flupirtine and limit my caffeine intake. Before I start taking it again I want to know:

1. Will taking Flupirtine for an extended period of time definitely lower tinnitus, even after the treatment is stopped?
   
   
2. How is taking Flupirtine for an extended period of time going to change my hyperacusis? Will I only experience less pain symptoms? Will I also be less vulnerable to setbacks? What can I expect?
   
   
3. Can Flupirtine be used after exposure to loud sounds to avoid a hyperacusis setback?
   
   
4. How long should we be taking Flupirtine for? @attheedgeofscience took for a couple of months (?), some girl on a German forum took it for a whole year for her tinnitus. Someone tried it for 2 weeks and said it didn't actually last. When I ordered this stuff I was under the impression that taking it for three months would be sufficient.
   
   
5. How does Flupirtine in terms of side effects and effectiveness in treating tinnitus compare to upcoming treatments?
   
   
6. What is the right dosage for long term treatment? Is 400 mg necessary or are slightly lower doses also sufficient?
   
   
7. For longer term treatment, is it alright to take a pause in taking Flupirtine for a period or time, or does that nullify the progress you've made in treating it?
   
   
8. Are there any long term dangers associated with taking GABAA modulation drugs?
   
   
9. Most importantly: How can I prevent the negative mental health side effects of taking Flupirtine?

Today I am not going to investigate these questions further. I am going to do my work, relax, and try to not think about my situation as much.

Like I said, an experience report is coming about, but I am done with Flupirtine for the moment until these questions are answered by someone with the right knowledge or experience. I am not going to put my liver and sanity on the line until I know more clearly what the long-term benefits of taking Flupirtine are. If anyone would be bothered to make a call or write an email to someone, I would greatly appreciate it. I am just not capable of being both the researcher and the guinea pig.

 

[StoneInFocus]

I'm too fucked up now to give a more elaborate response, but yesterday I took just 100 mg and my tinnitus is louder than ever now.

Mere moments ago I was contemplating about taking my life again.

I don't know how much of this can be attributed to the Flupirtine, but don't ever take this shit without consultancy of a professional if you're suicidal or can't mentally handle a spike. Don't underestimate how psychoactive this is. Suicidal ideation can appear as quick as lightning.

Pray for me.

 

[Matchbox]

I thought Kv 7.2/3 channels are specific to tinnitus?

My understanding was Kv 7.1 was more important and that's just in rat models plus Trobalt bound tighter to those.

Buuuuut it's been a long time since I've read up on this one and my sources are unavailable ever since so I'm recalling out my ass. I found out Trobalt was basically unfindable and there were safer lower dose versions in the pipe.

 

[Diego LR]

Hi @StoneInFocus,

I hope you are doing ok. I send you lots of positive vibes.

 

[Travis Henry]

I'm too fucked up now to give a more elaborate response, but yesterday I took just 100 mg and my tinnitus is louder than ever now.

Mere moments ago I was contemplating about taking my life again.

I don't know how much of this can be attributed to the Flupirtine, but don't ever take this shit without consultancy of a professional if you're suicidal or can't mentally handle a spike. Don't underestimate how psychoactive this is. Suicidal ideation can appear as quick as lightning.

Pray for me.

Praying for you my brother!

Let us know if you are ok.

 

[StoneInFocus]

UPDATE:

First of all I want to thank everyone for their prayers, vibes, kind words and digital hugs. Even though we're all total strangers and I am only a part-time believer, I really appreciate these tokens of support.

As you may have read I experienced a tinnitus spike on Monday. I also suffered from a nervous breakdown. From Monday to Wednesday I was pretty much in survival mode because of the catastrophic tinnitus.

Luckily I'm doing so much better now. I think my tinnitus volume is now back to its pre-Flupirtine state, and I am no longer really bothered by my tinnitus anymore. The most important factor in my healing was probably the strenuous exercise, which consisted of lower and upper body strength training.

In my opinion, heavy exercise, the type of activity that greatly tires you out and makes your muscles sore, is one of the most, if not the most crucial element in not only how you experience your tinnitus, but also in the building and maintenance of your entire physical (1), mental (2) and spiritual well being (3). And by 'spiritual' I don't just mean worshiping a God or other types of religious activity, this term encompasses more than that. It encompasses questions like; which things in this life are worth fighting for? What do I think beauty is? How do I want to be remembered? What kind of influence do I want to have on other people? I believe the most important thing we can do is upgrade ourselves on these three dimensions of our being, regardless if we have tinnitus or not. Remember how, when we (or at least a lot of people) are just awake, our tinnitus seems much quieter, and when we are tired or in a bad mood, it seems much louder. I think it all has something to do with our general energy or fitness levels. If we raise these levels high enough, I think it's possible to completely obliterate our tinnitus, or at least bring it down to a very low level. I think if we look at just 1 specific medicine for our tinnitus we are looking at our condition too narrowly. It's just something to think about. I also want to warn about spending too much time on this forum, or even behind a screen for that matter.

Nevertheless, I am still determined to take Flupirtine. Not necessarily for my tinnitus, but more so for my noxacusis, as the latter condition seems much more difficult to improve. If I can make my mind more powerful I can prevent it from breaking from the Flupirtine. I don't know how long this is going to take but I'm pretty hopeful I will get there someday. I am seeing a doctor next week, who recommended me 3-4 grams of NAC daily to protect the liver. I want to figure out, besides strengthening my mind, how I can avoid the negative mental side effects of Flupirtine.

I will give an update next week. Let's hope the doctor can help me out.

 

[addot]

My understanding was Kv 7.1 was more important and that's just in rat models plus Trobalt bound tighter to those.

According to Thanos Tzounopoulos, Kv 7.2 and Kv 7.3 are the most important ones.

More sources:

Transient Delivery of a KCNQ2/3-Specific Channel Activator 1 Week After Noise Trauma Mitigates Noise-Induced Tinnitus

Potent KCNQ2/3-specific channel activator suppresses in vivo epileptic activity and prevents the development of tinnitus

Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus

Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus

 

[Matchbox]

According to Thanos Tzounopoulos, Kv 7.2 and Kv 7.3 are the most important ones.

More sources:

Transient Delivery of a KCNQ2/3-Specific Channel Activator 1 Week After Noise Trauma Mitigates Noise-Induced Tinnitus

Potent KCNQ2/3-specific channel activator suppresses in vivo epileptic activity and prevents the development of tinnitus

Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus

Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus

Thank you. I stand corrected.

 

[Cory_]

UPDATE:

[all that]

What a relief!

 

[Ela Stefan]

UPDATE:

First of all I want to thank everyone for their prayers, vibes, kind words and digital hugs. Even though we're all total strangers and I am only a part-time believer, I really appreciate these tokens of support.

As you may have read I experienced a tinnitus spike on Monday. I also suffered from a nervous breakdown. From Monday to Wednesday I was pretty much in survival mode because of the catastrophic tinnitus.

Luckily I'm doing so much better now. I think my tinnitus volume is now back to its pre-Flupirtine state, and I am no longer really bothered by my tinnitus anymore. The most important factor in my healing was probably the strenuous exercise, which consisted of lower and upper body strength training.

In my opinion, heavy exercise, the type of activity that greatly tires you out and makes your muscles sore, is one of the most, if not the most crucial element in not only how you experience your tinnitus, but also in the building and maintenance of your entire physical (1), mental (2) and spiritual well being (3). And by 'spiritual' I don't just mean worshiping a God or other types of religious activity, this term encompasses more than that. It encompasses questions like; which things in this life are worth fighting for? What do I think beauty is? How do I want to be remembered? What kind of influence do I want to have on other people? I believe the most important thing we can do is upgrade ourselves on these three dimensions of our being, regardless if we have tinnitus or not. Remember how, when we (or at least a lot of people) are just awake, our tinnitus seems much quieter, and when we are tired or in a bad mood, it seems much louder. I think it all has something to do with our general energy or fitness levels. If we raise these levels high enough, I think it's possible to completely obliterate our tinnitus, or at least bring it down to a very low level. I think if we look at just 1 specific medicine for our tinnitus we are looking at our condition too narrowly. It's just something to think about. I also want to warn about spending too much time on this forum, or even behind a screen for that matter.

Nevertheless, I am still determined to take Flupirtine. Not necessarily for my tinnitus, but more so for my noxacusis, as the latter condition seems much more difficult to improve. If I can make my mind more powerful I can prevent it from breaking from the Flupirtine. I don't know how long this is going to take but I'm pretty hopeful I will get there someday. I am seeing a doctor next week, who recommended me 3-4 grams of NAC daily to protect the liver. I want to figure out, besides strengthening my mind, how I can avoid the negative mental side effects of Flupirtine.

I will give an update next week. Let's hope the doctor can help me out.

Did you try Flupirtine?

 

[StoneInFocus]

Did you try Flupirtine?

If you mean whether or not I've ever tried Flupirtine again, no I have not.

Right now my focus is on cannabidiol. We'll see how that goes.

 

[bobthebuilder]

If you mean whether or not I've ever tried Flupirtine again, no I have not.

Right now my focus is on cannabidiol. We'll see how that goes.

Godspeed. Agree the NAC could help mitigate damage if you were to try it again, especially for a longer period. I take 1.2g per day and have noticed that tinnitus spikes from unexpected loud noise exposures last far less longer now than they used to (1-2 days, rather than a week), presumably because of the antioxidant and anti-inflammatory effects.

 

[Ela Stefan]

Godspeed. Agree the NAC could help mitigate damage if you were to try it again, especially for a longer period. I take 1.2g per day and have noticed that tinnitus spikes from unexpected loud noise exposures last far less longer now than they used to (1-2 days, rather than a week), presumably because of the antioxidant and anti-inflammatory effects.

For how long did you take the NAC?

 

[bobthebuilder]

For how long did you take the NAC?

Two months now.

 

[ZFire]

Godspeed. Agree the NAC could help mitigate damage if you were to try it again, especially for a longer period. I take 1.2g per day and have noticed that tinnitus spikes from unexpected loud noise exposures last far less longer now than they used to (1-2 days, rather than a week), presumably because of the antioxidant and anti-inflammatory effects.

Wow, interesting... This is quite similar to what I've been experiencing lately with NAC since starting it 2 months ago also. There's this reactive tone I have that comes on every now and then. Pre-NAC, this reactive tone would stay with me for at least 1-2 weeks. But ever since I started taking NAC (1200mg), this reactive tone only lasts for 1-2 days now. Actually, I don't hear this reactive tone much anymore. And when I do, it's very short lived. This can't be a coincidence.

 

[StoneInFocus]

Recap: I have taken 200 mg on Tuesday and 400 mg on Wednesday, both all the pills at once.

Thursday I had taken 100 mg around noon, and 300 mg around the late afternoon.

I think I might have overdone it. Reading this leaflet I get the impression that you're only supposed to take Flupirtine at maximum 200 mg at once.

Combine reckless dosing with alcohol use and an unstable mind, and I kind of understand why my Flupirtine experiment went so horribly wrong.

I don't really see how Kv7 channel opening, NMDA antagonism or the increased susceptibility of GABAA receptors can worsen tinnitus on their own. Maybe it could but how that would work is something I'd have to investigate yet.

It's interesting to think about the role of Kv7.4 in the excitability of outer hair cells and the glutamate transmission to type II afferent SGNs.

I have a few more credentials at hand that allow more resources

Hey @Matchbox, do you mind if I ask you a question?

In this paper, it is said that "At concentrations of 10 µM, all openers except flupirtine strongly increased steady-state KCNQ4 currents (at 0 mV) 4- to 12-fold. In these experiments the rank order of current potentiation was: flupirtine < retigabine < BMS-204352 < ZnP < ZnP/Ret. Despite different degrees of current augmentation, heterologous KCNQ4 showed comparable sensitivities for flupirtine (EC50= 2.9 µM), retigabine (EC50= 3.7 µM), BMS-204352 (EC50= 3.5 µM), and for ZnP (EC50= 6.8 µM)."

If EC50 concentrations of all compounds are roughly similar (with Flupirtine even having the lowest), how is it that Flupirtine has the lowest KCNQ4 current potentiation?

BTW, do you have some understanding of how you could translate these in vitro EC50 values to a human dose to achieve the same effect?

 

[ajc]

Combine reckless dosing with alcohol use and an unstable mind, and I kind of understand why my Flupirtine experiment went so horribly wrong.

Would you consider re-trying it?

 

[StoneInFocus]

Would you consider re-trying it?

It's definitely something I'm considering.

As a matter of fact, I already took a couple 'test drives' with 100 mg QD about a week ago. I feel that 3 to 4 pills a day should be doable.

I am still not entirely sure whether regular Flupirtine doses will have sufficient effect on the potassium channels of the type II SGNs to treat my noxacusis.

I am also a bit worried about potential liver damage, although Flupirtine has been reported to be safe for a treatment period of at least a year. The current advice is to not take it for longer than two consecutive weeks.

The retailer where I bought the Flupirtine also doesn't seem to sell it anymore. I still have a few hundred pills left, enough to last me 1 to 2 months.

If everything is alright, I will be visiting a pain specialist next week, who also specializes in treating tinnitus. I'll discuss taking Flupirtine with him.

 

[StoneInFocus]

The retailer where I bought the Flupirtine also doesn't seem to sell it anymore. I still have a few hundred pills left, enough to last me 1 to 2 months.

I just emailed the retailer to ask when Flupirtine will be back in stock. He said never as he claimed it is not manufactured anymore.

 

[BB23]

I just emailed the retailer to ask when Flupirtine will be back in stock. He said never as he claimed it is not manufactured anymore.

Any more updates to your experiment with Flupirtine? I myself am considering taking some as well...

 

[StoneInFocus]

Any more updates to your experiment with Flupirtine? I myself am considering taking some as well...

So far, for protection, I have taken 4 to 6 pills (while on Flunarizine or Carbamazepine) on days when I had to travel with public transport for many hours. Not sure if it helped. Taking these pills did not spike my tinnitus, but maybe that only happens after using Flupirtine for several days in a row like last time.

As I'm currently on Carbamazepine, I'm only planning to use Flupirtine incidentally for the time being. I want to be economical with my stack because I haven't found a supplier yet that I trust.

 

[BB23]

So far, for protection, I have taken 4 to 6 pills (while on Flunarizine or Carbamazepine) on days when I had to travel with public transport for many hours. Not sure if it helped. Taking these pills did not spike my tinnitus, but maybe that only happens after using Flupirtine for several days in a row like last time.

As I'm currently on Carbamazepine, I'm only planning to use Flupirtine incidentally for the time being. I want to be economical with my stack because I haven't found a supplier yet that I trust.

I have a GABA issue due to Fluoroquinolone intoxication + Mirtazapine messing up with my Serotonin causing my tinnitus and hyperacusis along with TTTS. It has improved so much from the beginning but the progression stopped and it's been like this for months.

My ex-girlfriend, who is in Thailand, was able to get Flupirtine for me from India, she will bring it when she visits me next month or so, but I'm scared to take it in my current state, since Flupirtine can also mess with GABA receptors and I unfortunately got some visual snow due to being on Mirtazapine. I'll keep it just in case I can't take the noise anymore. I'm actually looking forward to BHV-7000 more since it doesn't have much GABA affinity...