Reformulated Retigabine (Trobalt): BHV-7000, a Kv7.2 Modulator by Biohaven (Pfizer)
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From my experience, Retigabine tablets are not divisible in themselves, but with a scalpel and a small precision scale you can do it with an acceptable margin of error.
According to this paper, Kv7.5 is heavily expressed in the auditory brain. I hope it doesn't play a role in tinnitus maintenance...
The potassium channel KCNQ5/Kv7.5 is localized in synaptic endings of auditory brainstem nuclei of the rat
Also, there's another company, Eliem Theraputics, coming out with a Kv7.2/7.3 modulator, codenamed ETX-123, Phase 1 beginning in 1H 2024. From the figures posted in the below presentation, it binds to Kv7.2/3 and Kv7.3/5 more potently than XEN1101...
Eliem Therapeutics: Clinical Stage Neurology Company Focused on Neuronal Excitability Disorders (PDF)
The potassium channel KCNQ5/Kv7.5 is localized in synaptic endings of auditory brainstem nuclei of the rat
Also, there's another company, Eliem Theraputics, coming out with a Kv7.2/7.3 modulator, codenamed ETX-123, Phase 1 beginning in 1H 2024. From the figures posted in the below presentation, it binds to Kv7.2/3 and Kv7.3/5 more potently than XEN1101...
Eliem Therapeutics: Clinical Stage Neurology Company Focused on Neuronal Excitability Disorders (PDF)
- Nov 2, 2022
- 440
- Tinnitus Since
- 09/2022
- Cause of Tinnitus
- Ear infection/Ultra High Frequency SSHL in Right Ear
Thanks a lot for sharing this. I feel like a new Research News thread could be started for Eliem Therapeutics. I really like how they continually state "Neuronal Excitability Disorders" on the website and as their target, which tinnitus absolutely is, but they don't mention tinnitus as a specific area to target. Maybe an email inquiring about it might give us an idea if it's on their radar at all.
It's so crazy to me how we literally have nothing now, but in 3-5 years we could have more than one option that could potentially help so many of us. Just gotta figure out how to make it until then
It helped my somatic tinnitus, yes, it 90% vanished for 1 hour.
It probably did something for the non-somatic tinnitus, but far less than for my somatic tinnitus.
But I remember I was one day basically tinnitus-free for 1 hour, i.e. impossible to hear it unless being in perfectly silent room.
Indeed.
I got tinnitus in August 2020.
I started first Retigabine experiment in January 2023 but without real success. My first success is in May 2023 and my best treatment session is in August 2023, so 3 years after onset.
1 hour of respite from what dose? It sounds impractical to take even if there were no side effects...
300 mg and 400 mg.
It's very random, sometimes 300 mg works better than 400 mg etc, but under 300 mg there are no effects at all.
Side effects are pretty heavy but manageable.
Yes, not very convenient.
My best hope with Retigabine is to get definitive effects with a cure of 3 months max.
In any case, we need a reformulation.
I may be joining you in this experiment next month.
Do you take it as in like someone would take an Aspirin? Or three times a day?
Does the tinnitus suddenly return after an hour or is the increase gradual?
My concern with these potassium channel modulators is they may be too selective. In other words, it's the wide spectrum of Trobalt that makes it effective for many. Yes, I know what the literature shows but it's animal models and relates to acute tinnitus. It also doesn't directly imply causation as it is just a finding so to speak.
Both.
In January I took it x3/day for 2 weeks; it worked only 2 times.
I adopted an Aspirin approach, x2-3 per week in the month of May; 100% of success.
In August I tried x3 per day for 1 month; most doses worked but it was pretty random.
I recommend taking it on an empty stomach.
The tinnitus slowly returns to baseline, but it tends to be weaker for a few hours, which may be the placebo effect.
You share my concerns too. You summed it up well, but we can't be sure of it yet.
Thanks for your detailed reply @Kleiner. It's very interesting.
Did you get the common side effects like dizziness and confusion for a few hours?
Yes, this has always been the case so far, from almost nothing to heavy side effects. Most of the time it is a state comparable to alcohol psychologically, but without the effects of nausea and such. And it's very selective.
For example, I have a lot of trouble organizing my thoughts, but not walking, while having some difficulty orienting myself in space, and with a really strange perception of time.
Retigabine must act on certain brain centers and others not, where alcohol will have a depressive effect on the entire system.
Generally these side effects also last 1 hour and tend to be at the same time as the main effect, but there are exceptions.
I had 5-6x heavier effects, psychoses, hallucinations, but I was in an unstable mental state and I was taking it with Gabapentin, so it was difficult to draw conclusions.
And it's better to avoid sports or driving while taking Retigabine.
To summarize, in the short term, I think the side effects are manageable. In the long term, no idea, but I remain very careful and I will never exceed 3 months of treatment.
Hahaha, bloody hell, you're not convincing me much @Kleiner, although some people pay good money for LSD and acid. I only hope I can achieve some efficacy at lower doses, like some people did. I suppose knowing the side effects only last a short time helps. I remember, just about, how spaced I was the first time I took 300 mg of Gabapentin. I was bouncing off walls.
These heavy side effects were also associated with Gabapentin and my emotional state so it's hard to be sure. I prefer to warn when in the doubt.
It's also quite comparable to acids/hallucinogens, the risk of "bad trip" and psychosis is mainly linked to your emotional state. That's what I felt at least.
You are right to start with a low dose, I did the same, but until 300 mg it had no effect at all, but I know some people got relief from 200 mg.
To be fair, I find Tramadol/opioids much more unpleasant in terms of side effects than Retigabine.
There's another product in the pipeline by Biohaven, BHV-8000, that addresses neuroinflammation by inhibiting TYK2/JAK1 signals. It will be trialled on Parkinson's patients in 2024. In their abstract, they said these signals play a role in diseases such as Parkinson's Disease, Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis.
We know from the past studies that neuroinflammation may play a role in tinnitus. Dr. De Ridder also says so.
"Tumor necrosis factor-alpha (TNFα) may promote neuroinflammation prompting tinnitus."
Do you guys think BHV-8000 may be helpful in tinnitus alleviation? Are there any studies linking TYK2/JAK1 signals to tinnitus?
We know from the past studies that neuroinflammation may play a role in tinnitus. Dr. De Ridder also says so.
"Tumor necrosis factor-alpha (TNFα) may promote neuroinflammation prompting tinnitus."
Do you guys think BHV-8000 may be helpful in tinnitus alleviation? Are there any studies linking TYK2/JAK1 signals to tinnitus?
I think neuroinflammation is hype generally. A buzzword. As for Dr. De Ridder, my respect for him has dwindled and his proposals for a 'War on Tinnitus' seem theoretical and not linked to much research.
Now when I say hype, I'm talking about tinnitus. Neuroinflammation may be linked to many diseases but for the vast majority with tinnitus it's a change in hearing function, temporary or permanent. A normal audiogram does not exclude you from this. Those without a history of loud noise exposure may have age-related hearing decline. There is little evidence I've seen that anti-inflammatory products resolve tinnitus, although they may reduce it a little in a select few.
I've said this for years about hearing tests. As someone who's been through the rigors of medical school, there is not a single OBJECTIVE test for hearing loss, only a subjective audiogram. It would be akin to walking into your ophthalmologist's office, reading the Snellen eye chart, and calling it a day. You may be able to read a line on the charger even though it's slightly blurry, but slight damage to our auditory system can be enough to trigger permanent tinnitus.
An eye doctor has several tests they can perform to assess vision disorders:
- Visual acuity test (as stated above)
- Retinoscopy
- Refraction test
- Keratometry test
- Peripheral visual field test
- Intraocular pressure measurement
- Digital retinal scans (which would be like an ENT literally getting an inside, digitally enhanced, look into our cochlea).
Take care.
Here's a study that show what happens to Kv7.2/7.3 channels after going through excitotoxicity. Basically at high Glutamate loads, the surrounding membrane engulfs the channels and it is said this action is IRREVERSIBLE. I don't like this. Maybe this is why Retigabine had sporadic results, because something is permanently lost inside...
Feel free to enlighten me.
Live Imaging of Kv7.2/7.3 Cell Surface Dynamics at the Axon Initial Segment: High Steady-State Stability and Calpain-Dependent Excitotoxic Downregulation Revealed
Feel free to enlighten me.
Live Imaging of Kv7.2/7.3 Cell Surface Dynamics at the Axon Initial Segment: High Steady-State Stability and Calpain-Dependent Excitotoxic Downregulation Revealed
Interesting.
This may be one of the explanations for why Retigabine doesn't work for everyone. But according to the anecdotes we have, it's mainly, in my opinion, a difference in generation site.
A good % of people benefit from Retigabine, at least a little, which indicates that their Kv7 channels are failing but still operational, if my understanding is correct.
There are many theories on the induction mechanism of tinnitus, which makes it difficult to make a conclusion.
- Mar 14, 2022
- 118
- Tinnitus Since
- 2017
- Cause of Tinnitus
- Long-term noise trauma
Have any studies or research been carried out into a possible link between increased Glutamate levels via sensory pathways other than sound (movement of the neck, jaw, etc.) stimulating/increasing tinnitus that is already present?
- Nov 2, 2022
- 440
- Tinnitus Since
- 09/2022
- Cause of Tinnitus
- Ear infection/Ultra High Frequency SSHL in Right Ear
Thanks for sharing. I'm no researcher or scientist so I don't know if it makes a difference when it comes to this, but I think something more positive to remember is the Biohaven and Xenon Pharmaceuticals drugs are said to be much more potent at these Kv7 channel sites than Retigabine. These are the first of their kind in terms of selection channels, potency, and (so far) reportedly way less side effect risk than Retigabine. Maybe these drugs will give relief for a significantly longer period of time while in system. Just me trying to be hopeful, I guess.
- Apr 6, 2020
- 1,031
- Tinnitus Since
- 2016
- Cause of Tinnitus
- 2016: headphones, 2020: worsened thanks to Rammstein
I emailed Dr. Tzounopoulos in 2020 concerning the state of potassium channels after acoustic damage (which can be the outcome of glutamate excitotoxicity).
Christiaan said:
Link: https://www.tinnitustalk.com/posts/531197/Dr. Tzounopoulos said:
This is food for thought and certainly may explain the scattergun, although generally efficacious result of Retigabine.
The issue is there is not a single study in humans.
It is funny that all these companies are talking about the retinal damage Retigabine caused and whatnot but STILL nobody has mentioned Retigabine also causing visual snow as a side effect, and how their newer compound eliminated this as a side effect.
Everybody here theorizes that opening Kv7.5 channels are to blame for this, but what if it is something else, God forbid what if it is the opening of Kv7.2/3? Remember, these drugs will mess with all channels in the brain, even the healthy functioning ones.
Although I'm thinking it was the GABA activity that caused visual snow with Retigabine, not one company is addressing anything regarding it. We still have so many unknowns here; it is going to be painful to wait years for prospects of positive results, which may not come...
Everybody here theorizes that opening Kv7.5 channels are to blame for this, but what if it is something else, God forbid what if it is the opening of Kv7.2/3? Remember, these drugs will mess with all channels in the brain, even the healthy functioning ones.
Although I'm thinking it was the GABA activity that caused visual snow with Retigabine, not one company is addressing anything regarding it. We still have so many unknowns here; it is going to be painful to wait years for prospects of positive results, which may not come...
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