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

[Aussie Lea]

You guys are seriously going to have this manufactured in China before the commencement of the human trials?

That is a risky proposition! caveat emptor

 

[Juan Carlos]

well is not like a totally new random drug. its a derivate from Trobalt, and on which creators state is targeting less (2 of 4) KV channels, therefore less side effects. Even thought I agree there is some risk involved, but the potentian benefits worth it for some people

 

[Bertman]

You guys are seriously going to have this manufactured in China before the commencement of the human trials?

That is a risky proposition! caveat emptor

I agree. With that said though, I hope everyone that goes through with it does so responsibly. I may be open to the idea later on, but at this time it's just too risky for me. I wish everyone the best and hopefully it works for you all.

 

[Supertramp]

I cannot believe what is being posted in this thread in the last few days. After the aut0063 disappointment, there is now possible new hope with RL648_81. So yes, let's ask the Chinese to steal and copy the formula and possibly negatively impact this research... and our hope that this ever results in a tested and approved medicin.

Keep going!

 

[Danny Boy]

I cannot believe what is being posted in this thread in the last few days. After the aut0063 disappointment, there is now possible new hope with RL648_81. So yes, let's ask the Chinese to steal and copy the formula and possibly negatively impact this research... and our hope that this ever results in a tested and approved medicin.

Keep going!

It shows the desperation people with tinnitus have. If it didn't take so long, people wouldn't have to do this. 10 years, heck 15, 20 years is an awful long time...Still with Autifony's drug, they believe there is a subgroup where it actually worked.

 

[Danny Boy]

You guys are seriously going to have this manufactured in China before the commencement of the human trials?

That is a risky proposition! caveat emptor

Hm...Well, it should have way less side-effects vs trobalt and we have no idea when this will even go to animal testing let alone come out. Have you got 10-15 years of waiting or 6 weeks which is how long it takes to get the drug the Chinese way?

 

[Supertramp]

Sure.
If Tinnitus Talk is found out to support drug piracy, then I'm sure that this new reputation will open all doors to future Tinnitus research.

As I said: keep going.

 

[attheedgeofscience]

I hope nobody bought Autifonys shares as there was a lot of talk about it

Autifony Therapeutics is not a publicly listed company. You can therefore not buy shares on the public stock market; you can only invest as an investor.

 

[Danny Boy]

Sure.
If Tinnitus Talk is found out to support drug piracy, then I'm sure that this new reputation will open all doors to future Tinnitus research.

As I said: keep going.

It has nothing to do with tinnitus talk, it's at its members own risks.

 

[madusmacus]

Although everyone is completely and blindly happy with all this...........IMO

People Need to stop talking about generic "Tinnitus"
Mine is NOT the same as yours

Mine is purple noise, bilateral somatic, manually modulatable tinnitus (neck jaw etc)
What's yours?...

You cant talk about treatment if every ones symptoms and causes are different - grrrr
No wonder all that doctors ever say is "you have tinnitus" live with it"

We don't ALL have the same thing and I'm sick of it </Rant Off>

P.S. sorry for being so down but I am really down

 

[Christian78]

Dr Inventor when I have mailed him and asked him about tests and people to apply for tests

"Chthonian - got your email, but there is not any clinical trial that I am aware of or will there be. Best, Thanos"

or

will post it in my website (http://www.audres.pitt.edu/people/tzounopoulos.php) when/if there is a clinical trial. Best, Thanos

He made pill but he is not sure in anything about it, it need to be started it is more that t suffers are making it becouse we need something to beleve. it is like Autifony happening again.

 

[linearb]

one thing to think about when preparing to consume undocumented analogs, is 1-methyl-4-phenyl-4-propionoxypiperidine vs 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

the world is full of peril.

 

[monacco]

Do you think that all searches that have been done by Dr Tzounopoulus during the last five years and at the end a chinese lab comes to copy the chimical Formula on the Pdf file and make easly a billon of dollars ? Is Dr Tzounopoulus stupid at this point ?

 

[linearb]

Do you think that all searches that have been done by Dr Tzounopoulus during the last five years and at the end a chinese lab comes to copy the chimical Formula on the Pdf file and make easly a billon of dollars ? Is Dr Tzounopoulus stupid at this point ?

A chinese lab is not going to make a billion dollars off this, and if a real drug ever comes anywhere near market, anyone selling a counterfeit will be aggressively prosecuted.

I personally know someone who had Suvorexant counterfeited overseas prior to US availability. Merck's stock price has not suffered as a result.

China is full of dodgy labs that do custom synthesis as a matter of course, in many cases providing wide catalogs of questionable things which are explicitly illegal in China itself (and a blind eye is no doubt turned when this is done for export only). If you saw the inside of these labs, you might think twice about consuming any of this stuff.

Independent GC/MS analysis in this case would be absolutely necessary -- but I'm curious where anyone expects such a lab to get a reference sample! I have a contact who has done GC/MS analytics of questionable "supplements" for me before; without a reference sample, the utility is... questionable.

 

[monacco]

He made pill but he is not sure in anything about it,

He Said that it is 15 times more portent than trobalt How did he know this so? Do you mean he did not know if it will work on humain or not?

 

[linearb]

He Said that it is 15 times more portent than trobalt How did he know this so? Do you mean he did not know if it will work on humain or not?

"potency" in this sense just refers to receptor affinity. The actual, subjective effects in humans are a question mark until it's trialed in humans.

 

[beeeep]

Still with Autifony's drug, they believe there is a subgroup where it actually worked.

Uhh, where did you find this information?

 

[monacco]

The actual, subjective effects in humans are a question mark

I am sur that it works ahh I remember the day when I took three pills of trobalt and went hunting I will not find this day in paradise

 

[dboy]

If you saw the inside of these labs, you might think twice about consuming any of this stuff.

Have you seen the inside of these labs? Apologies if I sound challenging, I just can't tell from your comment whether you are speaking from experience or conjecture? Also, were there problems with your friend's Suvorexant? Thanks for info.

 

[beeeep]

There's a good reason new drugs take so long until they even start Phase I studies.

http://www.sciencemag.org/news/2016/01/what-we-know-so-far-about-clinical-trial-disaster-france

A person died and several got serious brain damage during a phase I trial for a drug that "aimed at multiple disorders, including neurodegenerative diseases and anxiety". I think I read somewhere that by now there are even more fatalities, but I can't find that info a.t.m..

Also, I would be veeery careful about taking something that got synthesized in a shady lab somewhere. According to the above article, there might also be the chance that the drug was slightly impure (and remember, this stuff did not come out of some shady Chinese back ally).

The paper about RL658 surely is very interesting from a chemical point of view and I think that this kind of chemical research will speed up drug development quite a bit, but the tests they did used cultured cells in a petry dish, no one knows if this thing works at all or if it is not poisonous. You don't have to do a big chemical change to get from a harmless molecule to something poisonous. Sometimes you only have to change the chirality of the molecule...

 

[linearb]

Have you seen the inside of these labs? Apologies if I sound challenging, I just can't tell from your comment whether you are speaking from experience or conjecture? Also, were there problems with your friend's Suvorexant? Thanks for info.

http://www.vice.com/read/visiting-the-factories-in-china-where-synthetic-marijuana-gets-made

The labs pumping out the synthetic cannabinoids are, broadly, the same group of people doing custom synthesis of all kinds.

The suvorexant didn't kill my friend; it also GC/MS'd as what it was supposed to be, I believe. In that case a reference sample was available...

 

[dboy]

@linearb cheers.... interesting stuff.

 

[Kane Moffat]

Reading the discussion from the last few days has been both shocking and exciting. It seems pretty insane that some of you guys would take an untested drug from a supplier that is basically unregulated. The consequences could be catastrophic, as in, it might not kill you but give you a whole host of new CHRONIC problems in the brain and body.

I think it speaks volumes about the desperation some of us have as T sufferers, admittedly the idea of having to wait a decade for treatment is actually very scary- I have no idea how much worse mine could get in that time.

In contrast to this a time span of taking just a few months to find a drug that is safe and effective is almost like a fantasy, but it is surely an irrational action?

Assuming everything went fine, the lab in china produced the correct compound, the trial in mice didn't result in them all keeling over and dying, the human trial went ahead, had an effect, worked out the dosage and had not serious side effects. Can it then be guaranteed that this lab would produce a consistent product? Would it discourage legitimate research into K channel modulators? Is it even ethical to encourage other tinnitus sufferers to try this to get the cost down?

With all that being said, it would make one hell of a Tinnitus news story. 'Online group of Tinnitus sufferers decide the FDA were taking to long and cured themselves'.

 

[linearb]

Assuming everything went fine, the lab in china produced the correct compound, the trial in mice didn't result in them all keeling over and dying,

There wouldn't be a mouse trial, unless @Danny Boy or someone orders some mice online.

the human trial went ahead, had an effect, worked out the dosage and had not serious side effects.

self-experimentation with gray-market compounds would not produce useful data about the overall safety or effectiveness of the drug.

Can it then be guaranteed that this lab would produce a consistent product?

Absolutely not. These labs also fabricate a wide array of designer drugs, I can link you to all sorts of horror stories about bromo-dragonfly being sold as 2-C-B-Fly and other such things.

Would it discourage legitimate research into K channel modulators? Is it even ethical to encourage other tinnitus sufferers to try this to get the cost down?

I'd say no to both questions.

 

[matt89]

There wouldn't be a mouse trial, unless @Danny Boy or someone orders some mice online.

Provided that @Danny Boy purchases some mice online how can he find out if his mice are experiencing tinnitus after noise exposure?
Anyway I am voting for an accelerated RL-81 mouse trial led by Danny Boy.

Maybe we can set up a livestream to see how things are going on in the mice cage at Danny's home.

 

[matt89]

Unfortunately you cannot buy a mouse with pre-existing tinnitus.
https://www.jax.org/jax-mice-and-services/find-and-order-jax-mice
https://www.jax.org/mouse-search?searchTerm=tinnitus

I mean we need some mice with chronic T for this trial. Right @linearb?

 

[Joe Bananas]

Is my tinnitus finally making me crazy or is it true all that I am reading in here??
Guys, respect each other decisions as everybody in here knows a whole fuck**g lot about desperation. @Danny Boy , if you need a rodent, here I am. A 193cms, 90kgs rat. I'd give a try to anything reached this point. In fact I was about to give a try to 8grms of lead, single shot...

 

[Bobby B]

There are many firms in the USA or Europe which provide a whole catalog of research chemicals to research facilities or private labs. Molecules which haven't been yet released or approved .

Selleckchem is one of those which I have bought chemicals in the past .

The problem is that the prices are extremely high for very small amounts as their clients have big budget and funding.

They don't make these chemicals themselves - they buy them in bulk cheaper from China.

There is no legal issues with obtaining small amounts of research chemicals to test on yourself even in the USA and if this really works then of course the patent holders will be even more motivated to start working in order to have it eventually marketet in commercial approved form available to everyone.

The issue is that the cost and effort involved is huge and this is where it usually slows down to a snail pace.

The legal and cost issues arise when you test it on other people or market this as a treatment to other people.
Or when you "test" on yourself a drug which is on the list of forbidden substances like heroin...

RL is just a ion channel modulator similar to RTG and not even on any record yet

 

[Codaz]

Not to be very negative but we need much more than just a start of a drug research paper. Side effects, effects over time, duration, exclusion criteria. These drugs are so specific that it is even unclear what they do to your brain.

I was really really excited when reading about Trobalt / Retigabine and even thought about getting it. But then I heard about the side effects and the users for which it was not working or stopped working after a while.

So i'm sceptical to this one. I even wonder what is the difference in epileptic patients and tinnitus? It's not that we want to trade tinnitus for having an epileptic attack every week do we?

From my very limited knowledge about epilepsy it is something for which a definitive cure is not yet found. Patients that have these attacks take drugs for years, maybe even for the rest of their lives. Those drugs are in the same category that tinnitus patients take: the *pam drugs and keppra etc, see Wikipedia. Is that something that we want?
I've just read the side effects of epilepsy which can be horrible. To me, some of them are even more horrible than my T.

So if you guys want to be a Guinea pig, go ahead. But I'm sitting it out until there is much more known.

 

[Kotve]

Although everyone is completely and blindly happy with all this...........IMO

People Need to stop talking about generic "Tinnitus"
Mine is NOT the same as yours

Mine is purple noise, bilateral somatic, manually modulatable tinnitus (neck jaw etc)
What's yours?...

You cant talk about treatment if every ones symptoms and causes are different - grrrr
No wonder all that doctors ever say is "you have tinnitus" live with it"

We don't ALL have the same thing and I'm sick of it </Rant Off>

P.S. sorry for being so down but I am really down

Sure every T is due to a different factor, some ear, some neck and who knows about the rest. But the noise happens in the brain so if you find a way how to "stop" or reprogram the brain then you have found the master key.