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

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

    1. ruben ruiz

      ruben ruiz Member

      Location:
      Tucson, AZ
      Tinnitus Since:
      2012
      Cause of Tinnitus:
      I believe it was meds and stress
      Ive waited five years, Im spent. Not much left of me. Bless us all.
       
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    2. Penate

      Penate Member

      Tinnitus Since:
      07/04/2015
      People are just spoke with Professor thanos today and he told me it is no way that RL he's going to human trial a lease to next year he told me it is not in his hands no more light always in USA now depend in FDA another million of protocols and we can no spit results For the next four or five years.he was very clear to me it's not going to be any results to 2020 or 21 .thanos phone number-(412)383-8626.
       
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    3. valeri

      valeri Member Benefactor Hall of Fame

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      Thank you for contacting him but this answer has been heard from him before so...old news, bed news for us!

      Maybe we should start sending messages of desperation (end of my rope, can't do it anymore...) and obituaries to some of those people to get some attention!
       
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    4. lymebite
      Vegged out

      lymebite Member Benefactor

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    5. monacco

      monacco Member

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      forte Antoine .monaco
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      29/09/2015
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      anknown
      So it's better to wait stem celle therapy than this drug:(
       
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    6. Juan Carlos
      Whistles

      Juan Carlos Member Benefactor

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      Spain
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      02/2014
      Thats a horrible story, but it was totally preventable, i can see in spain we have an organization on wich we can analizy sustances for free http://energycontrol.org/ if you go in person, or for 30€ if you send it via mail
       
    7. Poyraz

      Poyraz Member

      Tinnitus Since:
      February 2016
      Cause of Tinnitus:
      Benzos, Stress, Anxiety, Loud Music, Jaw Problems. Who knows
      Someone should tell this professor that last night I was about to end my life. I was so ready to take whole box of the drug to end this pain. Man, I hate this world. I really do.
       
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    8. valeri

      valeri Member Benefactor Hall of Fame

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      I share your pain.
      I seriously wonder if they understand how damaging this game is for us who are living on the edge!
       
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    9. linearb
      Psychedelic

      linearb Member Benefactor Hall of Fame

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      again, to all the people saying that it would be easy to get a sample analyzed by a different lab:

      where do you propose to get a reference sample for GC/MS?
       
    10. Aussie Lea
      Dramaqueen

      Aussie Lea Member

      Location:
      Melbourne Yarra Valley
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      01/09/2013
      Can't the professor provide one?
       
    11. linearb
      Psychedelic

      linearb Member Benefactor Hall of Fame

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      I'm deeply skeptical that a clinical researcher would be willing to provide a sample of an experimental, patented substance to someone seeking to compare it to a bootlegged synthesis from a chinese lab.
       
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    12. Silvio Sabo
      Pooptoast

      Silvio Sabo Member Benefactor

      Location:
      Gothenburg, Sweden
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      05/2006
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      Noise - I think
      Deeply skeptical is one way of putting it..
       
    13. linearb
      Psychedelic

      linearb Member Benefactor Hall of Fame

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      I will once more encourage anyone considering consuming a research analog, to look at the differences between 1-methyl-4-phenyl-4-propionoxypiperidine vs 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. One of these things is not like the other.
       
    14. Bobby B
      Fine

      Bobby B Member Benefactor

      Tinnitus Since:
      11/2015
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      long term NIHL and recent acoustic trauma
      One solution would be to contact a lab in the US or Europe and ask them to synthesize a small amount which could be then used to compare to the Chinese lab version.

      They probably are going to charge a lot more though.

      I don't see a low risk - low cost - low waiting time solution here. There will be some compromises required.

      My personal perspective and experience dealing with these labs is that the research chemicals provided by the lab via my contact have been the real deal. And for years on.
      I have a medical issue which requires daily, long term constant medication and the commercially available/approved drugs don't work as well and some have side effects - like the RTG story in a way - but the "new- in test phase" drugs work much better and so far all the people who received those drugs from that Chinese lab have never been scammed or had issues with purity etc..so I may sound a lot more optimistic here.

      But yes - it will be tested and fed to animals too, and even we can find out if it reduces T in animals - the procedure is detailed in several studies. If it does - then chances are that this is the real drug not something else..and then purity can be easily tested too.
       
    15. Silvio Sabo
      Pooptoast

      Silvio Sabo Member Benefactor

      Location:
      Gothenburg, Sweden
      Tinnitus Since:
      05/2006
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      Noise - I think
      Anyone here in Sweden will surly know about the Neurosedyn scandal in the 1950's. A drug that was prescribed to pregnant women caused lots of children being born without arms and/or legs. The problem was not the active compound it was the fact that the chiral variant (called enantiomer) of the molecule had some horrifying effects.

      For those who don't know what chirality is, chirality is when a molecule has one or more chiral centers. A chral center is usually a carbon atom in the molecule that is asymmetric. Asymmetric meaning that it has bonds to several different structures. How these structures are bonded to the atom effects how they are related to each other. And this can have major impacts on the chemical properties of the molecule. A molecule can be either "left-" or "right-handed" (the word chiral is derived from the Greek word for hand). I will not go into details why they call it left or right handed since it has to do with the rules of in which order the structures are counted and the conventions of naming the enantiomers. But the simple explanation is that the molecule can be mirrored.

      In a mass spectrometer the two enantiomers will look identical since they contain the same structures and the same amount of the same kind of atoms. And they are normally created by the same chemical reactions. This means that when you synthesize a molecule in the lab you will normally have a distribution between the two. When creating one you will almost always create the other one at the same time as well.

      In the example with Neurosedyn the "real" compound was safe but the mirrored one was not. This is something many people don't know about but anyone that has studied organic chemistry will know. It's like the compound having an evil twin. I'm not sure if the shady Chinese labs are testing if they are obtaining the proper enantiomer of the compound since all the usual tests will not be able to tell them apart. And if they do, how will they know which one is the desired one?

      The usual way to tell them apart is the fact that two enantiomers of the same compound differ in their ability to rotate plane-polarized light.

      For those that are interested there is more about chirality of molecules here: https://en.wikipedia.org/wiki/Chirality_(chemistry)
       
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    16. Joe Bananas
      No Mood

      Joe Bananas Member

      Tinnitus Since:
      10/2015
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      Acoustic Trauma
      The sooner we assume we all are FUCKED UP the better...
       
    17. Penate

      Penate Member

      Tinnitus Since:
      07/04/2015
      OK this is the problem I was in my doctor today he's very honest with me he told me something I was relies long time ago does people selling hearing aids for 4000 $5000 they have to sell all these products before any Real medication get in the market is a real business they don't care if we kill himself they just want to sale on making money he told me it's a business and everybody is involved even the government so we have to stop by hearing aids and all that crap is never work otherwise we never going to get the real medication .
       
    18. undecided
      Breezy

      undecided Member

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      Greece
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      04/2014
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      Unknown.
      Organic chemistry is not necessary, anyone who has watched Breaking Bad knows about chirality.
       
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    19. Kane Moffat
      Badass

      Kane Moffat Member

      Location:
      Glasgow, Scotland
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      06/2015
      @Bobby B So how long do you think it will take you before you have this drug in your hand?
       
    20. valeri

      valeri Member Benefactor Hall of Fame

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      Aren't we better off having autifony drug reproduced in China?
      At least it's possible to obtain the original pill!
       
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    21. beeeep

      beeeep Member

      Location:
      Germany
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      ~2000, but real bad since 06/2015
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      B.t.w., just a quote from an article in the Time magazine with a leading Alzheimer researcher:

      "My biggest frustration is that we’ve cured Alzheimer’s in mice many times. Why can’t we move that success to people?” Longo says. (He’s referring to numerous promising compounds that have eliminated the amyloid plaques associated with Alzheimer’s in animals.)"

      Granted, it's about Alzheimer's, not T, but nevertheless, it holds true.

      AUT00063 also worked for mice. And this new compound hasn't even been tested on any animals yet...
      There's already quite a list of failed T drugs, not to mention many compounds that never made it out of the lab because they either didn't work or weren't save...
       
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    22. Silvio Sabo
      Pooptoast

      Silvio Sabo Member Benefactor

      Location:
      Gothenburg, Sweden
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      What everybody has to understand is that people are not mice! Although many things can be similar due to us both being mammals it's not exactly the same. The metabolism is not the same, the membrane proteins are not exactly the same which can effect how your molecule is absorbed by the cells for example. Then you have the blain blood barrier and so on and so on...

      Small differences can have huge impacts. Even between humans there are differences in reactions to drugs. Can you imagine the difference between two species that have a common ancestor that lived tens of millions of years ago!

      For example there is a fraction of the human population that are immune to HIV. This is because they have a mutation in one single gene that codes for a membrane receptor. The HIV binds to this receptor and enters the cell that way. In these people the virus cannot enter the cell which makes them immune. This is what can be the effect of a single mutation in one single gene! Imagine now the difference between a mouse and a man!

      We are talking about a huge complexity here. So just because a drug works in mice does not translate to that it will work the same in humans. If this was true then we wouldn't need any human trials!

      This is also why I stated in the AUT0063 thread that I don't understand why other primates are not utilized more in medical experiments. They are much more similar to us than mice. The only explanation is morality. But I have the opinion that it's far better that a few chimps suffer then hundreds of millions of people! Talk about immoral there!
       
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    23. Bobby B
      Fine

      Bobby B Member Benefactor

      Tinnitus Since:
      11/2015
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      long term NIHL and recent acoustic trauma
      I was thinking the same thing - why always use rats ? where I live they do sell monkeys in pet shops sometimes..I may as well get one or two, leave my audio full blast with AC/DC in loop while I am at work, come back and give the poor tinnitus suffering monkey some RL 81 to see what happens
       
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    24. Sarah Russett

      Sarah Russett Member

      Tinnitus Since:
      August 2015 - April 2017 (now T-free)
      Cause of Tinnitus:
      noise-induced
      Basically mice are less expensive and breed much faster than chimps. BUt I understand your question in terms of why wouldn'tthere be mice trials, then chimp trials, then human trials. But that would just slow everything down, I guess.
       
    25. Codaz

      Codaz Member

      But some of the noise is stopped by working on the neck and jaw, at least for me. So if the neck stays screwed then what?
       
    26. beeeep

      beeeep Member

      Location:
      Germany
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      ~2000, but real bad since 06/2015
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      Unknown
      There are tons of tests to be done before a drug can even enter human trials. Concerning the vast amount of potential drugs tested each year, I doubt there are even enough chimps around.

      Just take a look at page four of this publication by the Association of the British Pharmaceutical Industry.
      You need to screen thousands of drug candidates to get something that advances to pre-clinical trials. Here, only 1 in 10-20 candidates work out and advance to phase I trials at all and so on.

      Also, during pre-clinical trials, other animals (mainly dogs as far as I remember) are used, too.

      If animal tests are useful at all is an interesting area of discussion, anyway. Obviously they weren't that useful for AUT00063...
       
    27. Bobby B
      Fine

      Bobby B Member Benefactor

      Tinnitus Since:
      11/2015
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      long term NIHL and recent acoustic trauma
      The other issue is that the main target and market for RL is epilepsy..that's where they can make money as drugs are required on a daily basis and patients less scared of side effects due to the severity of the disease.
      Pharma firm don't like to sell drugs to perfectly healthy young people - very risky business.

      My point here is that we have no guarantee that this drug will be ever tested for T. Even if they go for human testing in many years eventually, it may be just for epilepsy and T will be put aside for later phases as its secondary.

      And for the monkeys - they cost around 2000 USD as pets..not cheap ! I don' think I would want to inflict noise damage to one.. but feed it some RL for a while would be a lot better than rats...given that the drug is expensive.
       
    28. Christian78
      Alone

      Christian78 Member

      Location:
      Gothenburg
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      (Sep 2013)
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      progressive tinnitus, time of expiring in next 3-6 months
      he made a chemical that is 15 times stronger (as you say), what or will it ever be used that remains to be seen, and if there will be then it will start with rats and after 1st human
      then 2 human
      then 3 human
      and 8 years, so no need to worry
       
    29. linearb
      Psychedelic

      linearb Member Benefactor Hall of Fame

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      this seems unlikely to be a miracle drug. It's a more targeted drug than RTG; I'd expect it to have less side effects, but that doesn't mean it's necessarily likely to work for people that RTG doesn't work for... and because it's never been tested in humans, taking it out of hope that it would be "safer" than RTG seems really misguided.

      RTG is hardly a miracle drug, either -- I think it should be studied more rigorously for tinnitus specifically, but the experience reports here, overall, do not overwhelm me. A small number of people have seen some significant improvement they attribute to the drug; a somewhat larger group experienced temporary relief on the drug; some people have seen no improvement, and some people have discontinued because of side effects. That doesn't seem much different than Clonazepam or a number of other drugs which have been trialed more extensively for tinnitus specifically.

      Have you taken Trobalt, @Bobby B?
       
    30. Bobby B
      Fine

      Bobby B Member Benefactor

      Tinnitus Since:
      11/2015
      Cause of Tinnitus:
      long term NIHL and recent acoustic trauma
      no I have not - my approach is to help heal the inner ear with LLLT as much as I can while its still "fixable" in the first months after trauma - the RGT side effects are just too strong since the T reduction requires a constant high dosage..this is not a long term solution that's why RL81 seems like a much better drug at least on paper.
       

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