From 6 or 7/10 to almost no tinnitus, unperceivable even in a quiet room with my fingers on my ears. It lasts for a few hours, while tinnitus comes back gradually.
RL648_81: Synthesis and Evaluation of Potent KCNQ2/3-specific Channel Activators
- Thread starter attheedgeofscience
- Start date
From 6 or 7/10 to almost no tinnitus, unperceivable even in a quiet room with my fingers on my ears. It lasts for a few hours, while tinnitus comes back gradually.
First time I took 3x300mg for like 3 months, give or take. I do think I developed some tolerance as it didn't lower my tinnitus anymore (it's difficult to measure tinnitus, you know), so I stopped because of this and side effects (it messes so much with your eyes. Luckily, all gone now). A couple of months later I started again with the same conclusions: lowered my tinnitus for a few months, then stopped because of tolerance and side effects.
ReyKalinic
Member
- Mar 3, 2016
- 89
- Tinnitus Since
- 2000
- Cause of Tinnitus
- Probably vestibular neuritis in summer 1999
Tolerance to retigabine in few months..... 
! who know how to do people with epilepsy! years and years without tolerance....
! who know how to do people with epilepsy! years and years without tolerance....
Was it effective from the first pill on or did you need to take it for a while before it helped?
Thanks. Thats interesting. I have some trobalt in my drawer but didn't try it yet. Anecdotes of permanent floaters freaked me out.
Currently I try pregabalin but when I finish I will give trobalt a short try.
Not so much to get relief, but just to know if it works for me like it does for you.
If it does it would probably convince me that my t originates from the nerves and not from my left ear hair cells. Not that it matters but since my onset I kept wondering and wondering and wondering...
Member- Mar 16, 2017
- 102
- Tinnitus Since
- 10/15 got worse 11/16
- Cause of Tinnitus
- Earbuds, inner ear infection NHL and high frequency loss
I am little worried about medication to treat this condition. Sure it sounds novel but your body might get used to it pretty fast and your messing with your brain. Hey I am all for it if no side-effects. What do others think?
- Apr 15, 2017
- 1,419
- Tinnitus Since
- 2008
- Cause of Tinnitus
- Noise
Not worth it until something comes to the market without any risky side effects.
Trobalt can turn your blue and milky man boobs
Trobalt can turn your blue and milky man boobs
- Apr 15, 2017
- 1,419
- Tinnitus Since
- 2008
- Cause of Tinnitus
- Noise
Trobalt what people were taking for tinnitus this and seizure drug, the side effects turned them blue and gave them a set of knockers, regardless to say, I haven't left the house since because I'm blue, but I've had a whale of a time playing with my new moobs
- Mar 16, 2017
- 102
- Tinnitus Since
- 10/15 got worse 11/16
- Cause of Tinnitus
- Earbuds, inner ear infection NHL and high frequency loss
We appreciate your interest in this compound and for your message. We have
not begun human testing for the compound yet. We are not able to provide
any forecast about when or if we will test this for tinnitus sufferers.
We have a corporate policy that precludes us from sharing such information
on an individual basis. I apologize but I cannot share more than that at
this time. We wish you the best in your pursuits.
Kind regards,
Bethany Worrell
--
Bethany Worrell
SciFluor Life Sciences LLC
300 Technology Square
Cambridge, MA 02139
bethany.worrell@scifluor.com
(w) 617-684-4748
Emailed them. Not sure if SF0043 is the same not much to say
not begun human testing for the compound yet. We are not able to provide
any forecast about when or if we will test this for tinnitus sufferers.
We have a corporate policy that precludes us from sharing such information
on an individual basis. I apologize but I cannot share more than that at
this time. We wish you the best in your pursuits.
Kind regards,
Bethany Worrell
--
Bethany Worrell
SciFluor Life Sciences LLC
300 Technology Square
Cambridge, MA 02139
bethany.worrell@scifluor.com
(w) 617-684-4748
Emailed them. Not sure if SF0043 is the same not much to say
- Apr 15, 2017
- 1,419
- Tinnitus Since
- 2008
- Cause of Tinnitus
- Noise
- Apr 15, 2017
- 1,419
- Tinnitus Since
- 2008
- Cause of Tinnitus
- Noise
- Aug 14, 2013
- 2,455
- Tinnitus Since
- Resolved since 2016
- Cause of Tinnitus
- Unknown (medication, head injury)
The intention is certainly to test RL-81 (a series of compounds) for efficacy vs. tinnitus. The problem tinnitus research is facing is that no pharma company is especially eager to take on a clinical trial pipeline related to tinnitus: the risk of failure (incl. false negative outcome) is too high.
Who knows... from a logical point of view one could expect that the pre-clinical study probably only focused on the neurochemical regulation of kv7.2-7.3 channels on cellular level.
Next step is to proof safety for use as a medicine (hence the analogs) and test it's efficacy on different conditions. This could be tinnitus (as Tzanoupolous theoritisized) or epilepsy (as a safer alternative for retigabine). It depends on which pharma corp gets the licence (and their projection of returning their investment).
@attheedgeofscience Is there something that we as a community can do to expedite this process? I am so sick of inaction, and If pharmaceutical companies won't help us, then we must revert to helping ourselves right?
How much does taking a medicine all the way though clinical testing cost? I know this is a big question and probably unrealistic. But maybe it's a discussion we need to have on here to form something?
How much does taking a medicine all the way though clinical testing cost? I know this is a big question and probably unrealistic. But maybe it's a discussion we need to have on here to form something?
- Apr 15, 2017
- 1,419
- Tinnitus Since
- 2008
- Cause of Tinnitus
- Noise
Suppose with any investment
Higher risk = Higher reward
Lower risk = lower reward
- Aug 14, 2013
- 2,455
- Tinnitus Since
- Resolved since 2016
- Cause of Tinnitus
- Unknown (medication, head injury)
If you are thinking of directly influencing the timeline of the clinical trial itself, then I don't believe there is anything that can be done considering:
- The willingness to contribute (or lack thereof) from the worldwide tinnitus community
- The monetary power (or lack thereof) from the worldwide tinnitus community
However, as it happens, almost a year ago, I did relay specific information that had come to my attention about RL-81 to a pharma company (and which is one of the four that have been approached about carrying the in vivo clinical research forward; at that point only in vitro studies had been done). Of course, this is kind of old news by now, but something I had not shared before (in public). For the same reasons, I can also confirm that Allergan is not one of the pharma entities in question (unlike what is suggested here recently):
It is fully understandable that slow progress can be frustrating. But finding effective treatments for medical conditions is not limited to tinnitus: there are many maladies that don't don't have good therapies. Tinnitus is but one of them...
The answer to how much it costs is:
- "It depends" (on the structure, screening, medical procedures involved, as well as the size of the clinical trial).
- "Lots of money".
- Aug 14, 2013
- 2,455
- Tinnitus Since
- Resolved since 2016
- Cause of Tinnitus
- Unknown (medication, head injury)
Yes: generally, an investor buying a "standard" investment e.g. one that you can invest in via a financial institution would ask for a higher return on investment (ROI) if it carries a higher risk. But investing in a clinical trial product candidate isn't a standard investment. And higher risk doesn't necessarily carry a higher reward (in this regard) because that would depend on the medical need and market cost (which determine the market value). Put another way: there are many other diseases (than tinnitus) that are worth pursuing therapies for and which at the same time would also be a good investment (due to high medical need). So from the investor point-of-view: why take a chance on finding a cure for tinnitus when there are so many other areas of interest that could be considered?
- Apr 15, 2017
- 1,419
- Tinnitus Since
- 2008
- Cause of Tinnitus
- Noise
Exactly. I was always planning to watch Auris closely if they succeeded, and to buy shares in them. Not anymore though unfortunately.
Unlike what you're implying here, I didn't make anything up. Couldn't you read the press release that I linked?
- Aug 14, 2013
- 2,455
- Tinnitus Since
- Resolved since 2016
- Cause of Tinnitus
- Unknown (medication, head injury)
Sure, I can read it: I have just now and also when it was released about a year ago. However, here is what you wrote:
And all I am saying is that RL-81 is not backed by big pharma and specifically not Allergan. In the press release, the material about potassium channels was unrelated to Allergan. SF0034 is backed by "small pharma" (not big pharma). A development for SF0034 (which sits with SciFluor) is scheduled later this year (but I will not bet anything on that pipeline before I see it "in action" - just as with Frequency Therapeutics...).
And what about trobalt / retigabine. Where those two medicines not backed by big pharma? And if that was so, why not back a redesigned drug that should work a lot better than the ones that they already backed? Was that just because the first two medicines weren't sold enough, and they see they might not be able to recoup their financial investment?
Pleasure_Paulie
Member
That compound was developed Glaxosmithkline (very very big pharma) and while I can't be sure, I would suspect that was removed due to poor performance in the market and an already oversaturated market for epilepsy pharmaceuticals. You can see their R&D pipeline here https://www.gsk.com/en-gb/investors/product-pipeline/
Perhaps there is a cilantro cure for tinnitus? Turns out cilantro is a natural KCNQ2/3 activator.
Cilantro leaf harbors a potent potassium channel–activating anticonvulsant
Published 16 July 2019
Rian Manville and Geoffrey Abbott
Abstract
Herbs have a long history of use as folk medicine anticonvulsants, yet the underlying mechanisms often remain unknown. Neuronal voltage-gated potassium channel subfamily Q (KCNQ) dysfunction can cause severe epileptic encephalopathies that are resistant to modern anticonvulsants. Here we report that cilantro (Coriandrum sativum), a widely used culinary herb that also exhibits antiepileptic and other therapeutic activities, is a highly potent KCNQ channel activator. Screening of cilantro leaf metabolites revealed that one, the long-chain fatty aldehyde (E)-2-dodecenal, activates multiple KCNQs, including the predominant neuronal isoform, KCNQ2/KCNQ3 [half maximal effective concentration (EC50), 60 ± 20 nM], and the predominant cardiac isoform, KCNQ1 in complexes with the type I transmembrane ancillary subunit (KCNE1) (EC50, 260 ± 100 nM). (E)-2-dodecenal also recapitulated the anticonvulsant action of cilantro, delaying pentylene tetrazole-induced seizures. In silico docking and mutagenesis studies identified the (E)-2-dodecenal binding site, juxtaposed between residues on the KCNQ S5 transmembrane segment and S4-5 linker. The results provide a molecular basis for the therapeutic actions of cilantro and indicate that this ubiquitous culinary herb is surprisingly influential upon clinically important KCNQ channels.
https://www.fasebj.org/doi/10.1096/fj.201900485R
Cilantro leaf harbors a potent potassium channel–activating anticonvulsant
Published 16 July 2019
Rian Manville and Geoffrey Abbott
Abstract
Herbs have a long history of use as folk medicine anticonvulsants, yet the underlying mechanisms often remain unknown. Neuronal voltage-gated potassium channel subfamily Q (KCNQ) dysfunction can cause severe epileptic encephalopathies that are resistant to modern anticonvulsants. Here we report that cilantro (Coriandrum sativum), a widely used culinary herb that also exhibits antiepileptic and other therapeutic activities, is a highly potent KCNQ channel activator. Screening of cilantro leaf metabolites revealed that one, the long-chain fatty aldehyde (E)-2-dodecenal, activates multiple KCNQs, including the predominant neuronal isoform, KCNQ2/KCNQ3 [half maximal effective concentration (EC50), 60 ± 20 nM], and the predominant cardiac isoform, KCNQ1 in complexes with the type I transmembrane ancillary subunit (KCNE1) (EC50, 260 ± 100 nM). (E)-2-dodecenal also recapitulated the anticonvulsant action of cilantro, delaying pentylene tetrazole-induced seizures. In silico docking and mutagenesis studies identified the (E)-2-dodecenal binding site, juxtaposed between residues on the KCNQ S5 transmembrane segment and S4-5 linker. The results provide a molecular basis for the therapeutic actions of cilantro and indicate that this ubiquitous culinary herb is surprisingly influential upon clinically important KCNQ channels.
https://www.fasebj.org/doi/10.1096/fj.201900485R
