RL648_81: Synthesis and Evaluation of Potent KCNQ2/3-specific Channel Activators

Discussion in 'Research News' started by attheedgeofscience, Mar 29, 2016.

    1. linearb
      Psychedelic

      linearb Member Benefactor Hall of Fame

      Location:
      beliefs are makyo and reality ignores them
      Tinnitus Since:
      1999
      Cause of Tinnitus:
      karma
      Cilantro is a natural chelator of some metals, so I went through a phase where I ate TONS of the stuff. Zero impact on tinnitus, but now I know how to make really good salsa and guac.
       
      • Informative Informative x 2
      • Like Like x 1
    2. Tigo

      Tigo Member

      Tinnitus Since:
      2 years
      Cause of Tinnitus:
      genetic hearing loss
      What happened to RL-81 made by SciFluor Life Sciences? Their website is offline...
      Is this again a dead end for a hopeful tinnitus treatment?
       
      • Good Question Good Question x 1
    3. Christiaan
      Inspired

      Christiaan Member Podcast Patron Benefactor Hall of Fame

      Location:
      The Hague, the Netherlands
      Tinnitus Since:
      2016
      Cause of Tinnitus:
      2016: headphones, 2020: worsened thanks to Rammstein
      It's too early to tell. Many people have mailed Dr. Tzounopoulos and he wrote them that the pre-clinical trials (on animals) have proven promising so far. And we know that they have the necessary financial backing to proceed to phase 1. Thus, there's no reason to think that there's a dead end at this early stage. Maybe they are updating the website for all we know.
       
    4. frpp

      frpp Member

      Tinnitus Since:
      2010
      Cause of Tinnitus:
      Tmj, Nihl, ototoxic drugs, nerve/ vascular issues
      Since these are epilepsy drug,s I wonder if they'll be able to stop spasms in the ear?
       
    5. Croaker
      Haunting

      Croaker Member Benefactor

      Tinnitus Since:
      01/2019 T, 04/2020 H
      Cause of Tinnitus:
      Headphones/Car Alarm/Immune Response?
      I think TTTS comes from the same signals that cause pain in hyperacusis, so I bet it will help.

      Very eager to see if anyone on here is able to get their hands on XEN-496 in the near future. I would warn anyone considering this that it is the same active molecule as in Trobalt. XEN-1101 is reformulated for fewer side effects but it won’t finish phase 2b testing until June 2022, although we can expect topline results in June 2021.
       
    6. Born To Slay
      Depressed

      Born To Slay Member

      Tinnitus Since:
      10/2019
      Cause of Tinnitus:
      Loud concert
      So XEN-496 isn’t different from Trobalt at all?
       
    7. weab00
      Gloomy

      weab00 Member Benefactor

      Location:
      Joe Dart's basement
      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      some good mf music
      Am wondering the same thing about side effects. I know that Trobalt caused visual snow syndrome in a number of people. Hopefully the negative side effects can be reduced. But we wouldn't know the long-term side effects until decades down the line. Although I'd gladly trade 5-10 years of lifespan for a tinnitus and hyperacusis-free life.
       
      • Like Like x 1
    8. GBB

      GBB Member Hall of Fame

      Location:
      NYC
      Tinnitus Since:
      2016-2019 (Mild, Cured) 8/2020 (Severe)
      Cause of Tinnitus:
      Virus / Microsuction / Acoustic Trauma
      Do you need to take Trobalt continuously? I've definitely seen stories on here where people have mentioned cessation or permanent improvement of their tinnitus from a "round" of Trobalt, so I've never been clear on that aspect.
       
    9. Croaker
      Haunting

      Croaker Member Benefactor

      Tinnitus Since:
      01/2019 T, 04/2020 H
      Cause of Tinnitus:
      Headphones/Car Alarm/Immune Response?
      Most of the anecdotes I’ve seen mentioned that relief was temporary.

      This makes sense if something is forcing the type II fibers or the bushy cells Dr. Shore mentioned to be sensitized. Regulating potassium channels doesn’t solve the fundamental problem.
       
    10. weab00
      Gloomy

      weab00 Member Benefactor

      Location:
      Joe Dart's basement
      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      some good mf music
      Wonder what this means with regards to setbacks and spikes. If you experienced an acoustic trauma while on a kV modulator would you experience pain/burning as long as you stayed on the medication? Guess it comes down to whether setbacks are physical damage or neuropathic pain.
       
    11. Croaker
      Haunting

      Croaker Member Benefactor

      Tinnitus Since:
      01/2019 T, 04/2020 H
      Cause of Tinnitus:
      Headphones/Car Alarm/Immune Response?
      I expect it would block most symptoms. It depends on how much more effective XEN-1101 is than Trobalt. I don’t think most setbacks are from physical damage.
       
    12. dan
      Chatty

      dan Member Hall of Fame

      Location:
      Toronto, Canada
      Tinnitus Since:
      06/2011
      Cause of Tinnitus:
      Loud noise
      Yes continuously, which causes irreversible organ damage/sudden death syndrome eventually.

      Why do you want to try it?
       
    13. weab00
      Gloomy

      weab00 Member Benefactor

      Location:
      Joe Dart's basement
      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      some good mf music
      Are you implying that's why @Danny Boy died?
       
    14. GBB

      GBB Member Hall of Fame

      Location:
      NYC
      Tinnitus Since:
      2016-2019 (Mild, Cured) 8/2020 (Severe)
      Cause of Tinnitus:
      Virus / Microsuction / Acoustic Trauma
      It would be more appealing if the effects could be cemented from a temporary regimen.
       
    15. dan
      Chatty

      dan Member Hall of Fame

      Location:
      Toronto, Canada
      Tinnitus Since:
      06/2011
      Cause of Tinnitus:
      Loud noise
      Very perceptive of you.... good news though, Prof. Thanos is addressing this issue with RL-81, he told me this himself. It's being tweaked.
       
    16. dan
      Chatty

      dan Member Hall of Fame

      Location:
      Toronto, Canada
      Tinnitus Since:
      06/2011
      Cause of Tinnitus:
      Loud noise
      Sorry for being so obtuse, I don't get it...
       
    17. GBB

      GBB Member Hall of Fame

      Location:
      NYC
      Tinnitus Since:
      2016-2019 (Mild, Cured) 8/2020 (Severe)
      Cause of Tinnitus:
      Virus / Microsuction / Acoustic Trauma
      I was answering honestly - you asked if I was considering it - I said it would be more attractive if I didn't need to take if forever. Anything that has wiped out tinnitus deserves to be considered imo.
       
      • Like Like x 1
    18. weab00
      Gloomy

      weab00 Member Benefactor

      Location:
      Joe Dart's basement
      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      some good mf music
      I too am wary of taking a novel seizure medication for life. But if it offers temporary relief I'd be all over it. I have a feeling regenerative medicine will be out before potassium channel modulators anyway, so hopefully we won't wind up needing it. Always good to have a second line of treatment though.
       
    19. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      Taking something once is of course going to be much more attractive and also much more beneficial in terms of safety. See this is why I think that the cochlear regeneration treatments are going to be better because you only need to take a small number of doses to complete the course and do not actually have to take it repeatedly to get and also actually maintain a benefit.
       
      • Agree Agree x 1
    20. AUTHOR
      AUTHOR
      attheedgeofscience
      No Mood

      attheedgeofscience Member Podcast Patron Mighty Benefactor Hall of Fame

      Location:
      Denmark
      Tinnitus Since:
      Resolved since 2016
      Cause of Tinnitus:
      See information page
      This thread was created more than five years ago (by yours truly) with no developments since then (as far as I know). However, earlier this year, an in vivo-study was released on RL-81 suggesting that the channel activator is effective at the preclinical stage. It would seem, therefore, that the timeframe between the in vitro- and in vivo- study has been some five years...

      The "non specific KCNQ channel activator" that is alluded to in the abstract is probably Trobalt.

      The above is not much. But, I thought I'd share it for those of you with an inclination for science updates. And given the lack of progress elsewhere in the pharma landscape, the above is perhaps worthwhile keeping an eye on. Contacting either Prof. Wipf or Prof. Tzounopoulos should be feasible (in order to understand next steps...).
       
      • Informative Informative x 2
      • Like Like x 1
      • Hug Hug x 1
    21. serendipity1996
      No Mood

      serendipity1996 Member Podcast Patron Hall of Fame

      Tinnitus Since:
      2011 - T, 2016- H, relapsed 2019
      Cause of Tinnitus:
      noise-induced
      Most of the discussion has been on Xenon Pharmaceuticals, which has developed a reformulated version of Retigabine with improved potency, safety, and selectivity. They already have two drug candidates in Phase 2b and Phase 3 of clinical trials.
       
      • Agree Agree x 2
      • Like Like x 1
      • Winner Winner x 1
      • Informative Informative x 1
    22. Matchbox
      Wishful

      Matchbox Member

      Location:
      BC Canada
      Tinnitus Since:
      August 2020
      Cause of Tinnitus:
      Noise Induced, Prednisone (drones), Barotrauma (distortions)
      I agree. Xenon is the winning horse right now even if it wasn't meant for tinnitus / hyperacusis.
       
    23. NewLionel

      NewLionel Member

      Tinnitus Since:
      2019
      Cause of Tinnitus:
      headphones
      Where/when do I get my hands on this stuff?
       
      • Like Like x 1
    24. AfroSnowman
      Balanced

      AfroSnowman Member Podcast Patron Benefactor

      Tinnitus Since:
      April 16 2019
      Cause of Tinnitus:
      Nonnatural energy source
      Is this a pill or injection?
       
      • Good Question Good Question x 1
    25. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      IV I think.
       
      • Good Question Good Question x 1

Share This Page