337 replies to this topic

[eon]

i'm really enjoying this thread.

[Flex]

 

Great Thread, thank you for creating it.

Just wondering how long it will take for those medications to actually become available to the broad public.

Also I'm pretty curious what scientists were doing the last 50-60 years, except for modifying and creating new kinds of SSRIs, since all those new types of medications are researched just now.

 

Some will take many years, as to what scientists were doing... I imagine a lot of time from the 80's through 2000 were spent doing research on SSRI's I am sure they thought that was it we cured depression.... at least for a bit.  I hear a lot of drugs do not make it through the FDA approval process so who knows how many of these breakthroughs will actually come to our homes one day..

 

 

Ask the Pharma companies.

Its up to them to develop and sell a new antidepressant, which is quiet expensive: 1 billion + ~ 10 years of clinical trials and approvement

Perhaps they didnt saw any advantage in the research substances, didnt wanted to see, the research wasnt that advanced & etc.

[eon]

That or they can skip it and take the nutraceutical route to skip the FDA garbage...

 

 

 

Great Thread, thank you for creating it.

Just wondering how long it will take for those medications to actually become available to the broad public.

Also I'm pretty curious what scientists were doing the last 50-60 years, except for modifying and creating new kinds of SSRIs, since all those new types of medications are researched just now.

 

Some will take many years, as to what scientists were doing... I imagine a lot of time from the 80's through 2000 were spent doing research on SSRI's I am sure they thought that was it we cured depression.... at least for a bit.  I hear a lot of drugs do not make it through the FDA approval process so who knows how many of these breakthroughs will actually come to our homes one day..

 

 

Ask the Pharma companies.

Its up to them to develop and sell a new antidepressant, which is quiet expensive: 1 billion + ~ 10 years of clinical trials and approvement

Perhaps they didnt saw any advantage in the research substances, didnt wanted to see, the research wasnt that advanced & etc.

 

 

[ILIkeBeer]

Manipulating Molecule in the Brain Improves Stress Response, New Target for Depression Treatment

 

http://newswise.com/...tsw-study-shows

 

[Joe Monroe]

 

Great Thread, thank you for creating it.

Just wondering how long it will take for those medications to actually become available to the broad public.

Also I'm pretty curious what scientists were doing the last 50-60 years, except for modifying and creating new kinds of SSRIs, since all those new types of medications are researched just now.

 

Some will take many years, as to what scientists were doing... I imagine a lot of time from the 80's through 2000 were spent doing research on SSRI's I am sure they thought that was it we cured depression.... at least for a bit.  I hear a lot of drugs do not make it through the FDA approval process so who knows how many of these breakthroughs will actually come to our homes one day..

 

Just wanted to point out that big pharma is not interested in finding cures. Their goal is to make money, they want to give people something they can take daily, for a lifetime and be dependent on it. If they actually cured diseases what kind of business model would that be? 

[Flex]

Would be interresting to see how they react when actually a cure comes out. I guess it will be something like in the case of E-Cigarettes and Tobacco industry.

You can notice this at the new EU laws from 2014/15 btw.

[rena123]

 

 

Great Thread, thank you for creating it.

Just wondering how long it will take for those medications to actually become available to the broad public.

Also I'm pretty curious what scientists were doing the last 50-60 years, except for modifying and creating new kinds of SSRIs, since all those new types of medications are researched just now.

 

Some will take many years, as to what scientists were doing... I imagine a lot of time from the 80's through 2000 were spent doing research on SSRI's I am sure they thought that was it we cured depression.... at least for a bit.  I hear a lot of drugs do not make it through the FDA approval process so who knows how many of these breakthroughs will actually come to our homes one day..

 

Just wanted to point out that big pharma is not interested in finding cures. Their goal is to make money, they want to give people something they can take daily, for a lifetime and be dependent on it. If they actually cured diseases what kind of business model would that be? 

 

Yeah unfortunately you're perfectly right. That's also what's depressing me the most everytime I see my psychiatrist, since I know I'm basically just a money cow for them. But not much I can do, since everything is better than having to feel like this all the time.

 

Would be interresting to see how they react when actually a cure comes out. I guess it will be something like in the case of E-Cigarettes and Tobacco industry.

You can notice this at the new EU laws from 2014/15 btw.

I kind of doubt there will be one, since proper research takes millions-billions of dollars and no company is willing to spend that unless there will be a profit bigger than that in sight, which a cure certainly doesn't have.

And I wouldn't really consider E-Cigs a cure, they are just as bad since they get you addicted to nicotine (=constant long term profit), maybe just healthier (although a lot of the chemicals in E-Liquids haven't even been studied for regular long term use as far as i know).
The reason they are making laws against them is because the tabacco industry isn't profiting from e-cigs, not because they are a cure, but hey maybe you meant just that and I missunderstood your post.

Edited by rena123, 28 July 2015 - 11:22 PM.

[Duchykins]

Most studies that will be funded about e-cigs will be focusing very heavily on their potential for harm.  

 

I doubt we'll be seeing any serious, large studies in our generation comparing traditional tobacco products to e-cigs, which would demonstrate the superiority of e-cigs over cigarettes for people who just insist on having the nicotine.  No one says e-cigs are safer than not consuming either product, only that e-cigs are safer than analogs.

 

They have already put out quite a bit of scary bullshit about e-cigs though.  Propylene glycol is a perfect example.  This is very commonly used as a solvent for prescription medications that need to be delivered via inhaler or in a liquid, or used as a humectant.  Asthmatics tolerate it just fine.  I once saw a documentary several years ago that put PG on a list of "known toxins," laughed my ass off and stopped listening to it. 

[Flex]

Yes I meant that ^^

The German departments are seemingly quiet occupied by lobbitsts.

 

So, therefore I assume that if a cure appears, there would come a whole campagne against it.

 

Btw: Metagene has found something very interresting:

 

Tipepidine increases dopamine level in the nucleus accumbens without methamphetamine-like behavioral sensitization
http://www.sciencedi...166432815000893

 

the activation of the VTA could relieve depressions, because:

 

Selective inhibition of VTA dopamine neurons induces a depression-like phenotype.

http://www.nature.co...re11740_F1.html

 

and enhancing the Hippocampus activates the Nucleus Accumbens which inhibits the inhibitory actions of the Pallidum to VTA Neurons

 

Glutamatergic Afferents from the Hippocampus to the Nucleus Accumbens Regulate Activity of Ventral Tegmental Area Dopamine Neurons

www.jneurosci.org/content/21/13/4915.full

 

Edit:

 

He found also that it inhibits GIRK channels (via D1 & adrenergic a2 activation!) which are also implicated into Depressions

 

Dont know whether I should post the original source( due to paranoia..), so I´m posting this which looks the same to me

A Novel Antidepressant-like Action of Drugs Possessing GIRK Channel Blocking Action in Rats
https://www.jstage.j.../130_5_699/_pdf

 

Deletion of GIRK2 Subunit of GIRK Channels Alters the 5-HT1A Receptor-Mediated Signaling and Results in a Depression-Resistant Behavior.

http://www.ncbi.nlm....pubmed/25956878

Edited by Flex, 28 July 2015 - 11:43 PM.

[jefferson]

You're kidding yourselves if you think "Big Pharma" wouldn't jump at the chance to patent a miracle depression drug. A drug that cured depression could make tens of billions of dollars. The reasons major companies aren't pursuing research in the area anymore are because of the extraordinary difficulty and expense in bringing new drugs to market. This is for many reasons, the failure of the monoaminergic hypothesis and corresponding lack of ideas on what molecular pathway to target for many years, ridiculously large and strengthening placebo effect, the cost of putting a drug through trials when the success rate is less than 15% or something, less investment in R&D by the federal government, complexity and incomplete understanding of the brain compared to other illnesses, the recession... etc.

 

There is no conspiracy in keeping people on prozac forever. You're really delusional if you think so, sorry. Just like with the Hepatitis C cure, even a "cure" you only needed to take once could recoup investments by pricing it for $10,000.

[Joe Monroe]

You're kidding yourselves if you think "Big Pharma" wouldn't jump at the chance to patent a miracle depression drug. A drug that cured depression could make tens of billions of dollars. The reasons major companies aren't pursuing research in the area anymore are because of the extraordinary difficulty and expense in bringing new drugs to market. This is for many reasons, the failure of the monoaminergic hypothesis and corresponding lack of ideas on what molecular pathway to target for many years, ridiculously large and strengthening placebo effect, the cost of putting a drug through trials when the success rate is less than 15% or something, less investment in R&D by the federal government, complexity and incomplete understanding of the brain compared to other illnesses, the recession... etc.

 

There is no conspiracy in keeping people on prozac forever. You're really delusional if you think so, sorry. Just like with the Hepatitis C cure, even a "cure" you only needed to take once could recoup investments by pricing it for $10,000.

 

What you have to be delusional if you think they could fetch 10k for one dose of a drug. Just look at ketamine it is not pushed at all by big pharma because ... why would they push something that cures depression in a matter of hours for often weeks?

 

If you just look at the roots of the traditional medicine in general it's completely fueled by the pharmaceutical industry, since 1913, when the rockefeller foundation was created. Rockefeller's oil monopoly was shutdown by the government so he pursued pharmaceuticals after that, completely changing the way the medical field operated. 

[Joe Monroe]

Manipulating Molecule in the Brain Improves Stress Response, New Target for Depression Treatment

 

http://newswise.com/...tsw-study-shows

 

interesting, I can't seem to find a specific drug they were using to block the enzyme. When i use wiki to view PDE4 blockers it shows a plethora of drugs. Looks promising though 

[jefferson]

 

You're kidding yourselves if you think "Big Pharma" wouldn't jump at the chance to patent a miracle depression drug. A drug that cured depression could make tens of billions of dollars. The reasons major companies aren't pursuing research in the area anymore are because of the extraordinary difficulty and expense in bringing new drugs to market. This is for many reasons, the failure of the monoaminergic hypothesis and corresponding lack of ideas on what molecular pathway to target for many years, ridiculously large and strengthening placebo effect, the cost of putting a drug through trials when the success rate is less than 15% or something, less investment in R&D by the federal government, complexity and incomplete understanding of the brain compared to other illnesses, the recession... etc.

 

There is no conspiracy in keeping people on prozac forever. You're really delusional if you think so, sorry. Just like with the Hepatitis C cure, even a "cure" you only needed to take once could recoup investments by pricing it for $10,000.

 

What you have to be delusional if you think they could fetch 10k for one dose of a drug. Just look at ketamine it is not pushed at all by big pharma because ... why would they push something that cures depression in a matter of hours for often weeks?

 

If you just look at the roots of the traditional medicine in general it's completely fueled by the pharmaceutical industry, since 1913, when the rockefeller foundation was created. Rockefeller's oil monopoly was shutdown by the government so he pursued pharmaceuticals after that, completely changing the way the medical field operated. 

 

 

Actually, Ketamine is not a cure. Everyone who takes it eventually relapses unless they take another dose, and another, and another. Nevertheless, Johnson and Johnson is trying to get an intranasal version of Ketamine approved. The reason more pharma companies aren't pursuing Ketamine itself is simply because it's not patentable. This does not prove "Big Pharma wants to keep us depressed", it only proves that they're interested in making money, and they can make money if they actually had reliable new antidepressants, which they don't. It's not like Merck has a locked vault somewhere with a miracle drug that they're not marketing because it's uneconomical. So take the Hep C cure, Sofosbuvir. It cures Hepatitis C in 3 months and costs $100,000. One can imagine a similar situation where a new AD cured depression in 3 months and costs a similar amount for people with intractable, long-term depression. Insurance would balk, but would pay for a lot of people, and Medicare would too.

[eon]

tipepidine seems interesting so who sells it? What I find ridiculous is methamphetamine always gets compared to with a hint that it is a bad drug, when if anything it's really the ultimate stimulant. Addictive yes, but there's a reason why it's the poster child in being "compared" or "likened" to some new unproven drug no one has ever heard of. I'm on an amphetamine called Vyvanse for ADHD and boy do I wish I was on meth (Desoxyn). I'd probably achieve more in 10 years that I ever would in 30-50 years. Life is short not to live it to the fullest.

 

Yes I meant that ^^

The German departments are seemingly quiet occupied by lobbitsts.

 

So, therefore I assume that if a cure appears, there would come a whole campagne against it.

 

Btw: Metagene has found something very interresting:

 

Tipepidine increases dopamine level in the nucleus accumbens without methamphetamine-like behavioral sensitization
http://www.sciencedi...166432815000893

 

the activation of the VTA could relieve depressions, because:

 

Selective inhibition of VTA dopamine neurons induces a depression-like phenotype.

http://www.nature.co...re11740_F1.html

 

and enhancing the Hippocampus activates the Nucleus Accumbens which inhibits the inhibitory actions of the Pallidum to VTA Neurons

 

Glutamatergic Afferents from the Hippocampus to the Nucleus Accumbens Regulate Activity of Ventral Tegmental Area Dopamine Neurons

www.jneurosci.org/content/21/13/4915.full

 

Edit:

 

He found also that it inhibits GIRK channels (via D1 & adrenergic a2 activation!) which are also implicated into Depressions

 

Dont know whether I should post the original source( due to paranoia..), so I´m posting this which looks the same to me

A Novel Antidepressant-like Action of Drugs Possessing GIRK Channel Blocking Action in Rats
https://www.jstage.j.../130_5_699/_pdf

 

Deletion of GIRK2 Subunit of GIRK Channels Alters the 5-HT1A Receptor-Mediated Signaling and Results in a Depression-Resistant Behavior.

http://www.ncbi.nlm....pubmed/25956878

 

[eon]

So hep C has a cure? My mom has Hep C and have told me there is no cure for it. I believe she said she is on Entecavir for the rest of her life. I'd have to tell her about this Hep C cure for $100,000. Is this true?

 

 

 

You're kidding yourselves if you think "Big Pharma" wouldn't jump at the chance to patent a miracle depression drug. A drug that cured depression could make tens of billions of dollars. The reasons major companies aren't pursuing research in the area anymore are because of the extraordinary difficulty and expense in bringing new drugs to market. This is for many reasons, the failure of the monoaminergic hypothesis and corresponding lack of ideas on what molecular pathway to target for many years, ridiculously large and strengthening placebo effect, the cost of putting a drug through trials when the success rate is less than 15% or something, less investment in R&D by the federal government, complexity and incomplete understanding of the brain compared to other illnesses, the recession... etc.

 

There is no conspiracy in keeping people on prozac forever. You're really delusional if you think so, sorry. Just like with the Hepatitis C cure, even a "cure" you only needed to take once could recoup investments by pricing it for $10,000.

 

What you have to be delusional if you think they could fetch 10k for one dose of a drug. Just look at ketamine it is not pushed at all by big pharma because ... why would they push something that cures depression in a matter of hours for often weeks?

 

If you just look at the roots of the traditional medicine in general it's completely fueled by the pharmaceutical industry, since 1913, when the rockefeller foundation was created. Rockefeller's oil monopoly was shutdown by the government so he pursued pharmaceuticals after that, completely changing the way the medical field operated. 

 

 

Actually, Ketamine is not a cure. Everyone who takes it eventually relapses unless they take another dose, and another, and another. Nevertheless, Johnson and Johnson is trying to get an intranasal version of Ketamine approved. The reason more pharma companies aren't pursuing Ketamine itself is simply because it's not patentable. This does not prove "Big Pharma wants to keep us depressed", it only proves that they're interested in making money, and they can make money if they actually had reliable new antidepressants, which they don't. It's not like Merck has a locked vault somewhere with a miracle drug that they're not marketing because it's uneconomical. So take the Hep C cure, Sofosbuvir. It cures Hepatitis C in 3 months and costs $100,000. One can imagine a similar situation where a new AD cured depression in 3 months and costs a similar amount for people with intractable, long-term depression. Insurance would balk, but would pay for a lot of people, and Medicare would too.

 

 

[Duchykins]

Eon, there will always be scientists out there who are genuinely working hard to solve the world's problems.  There will always be some idealists sprinkling all the fields who are not puppets of "Big Pharma"^TM or any other major institution.    The are always scientists who are keenly interested in one or two particular things and will take on a cause that could last them their whole lives.  While that doesn't necessarily mean they have as many resources, that doesn't mean they give up or have no power at all.

[jefferson]

Entecavir is used to treat Hepatitis B. There is no cure for Hep B, but I would bet there will be in the near future. There is already a candidate for a cure in clinical trials. http://www.scienceda...50420154819.htm

[eon]

I see. My mom has Hep B, not Hep C, I had it confused.

 

 

Entecavir is used to treat Hepatitis B. There is no cure for Hep B, but I would bet there will be in the near future. There is already a candidate for a cure in clinical trials. http://www.scienceda...50420154819.htm

 

[Shai Hulud]

Manipulating Molecule in the Brain Improves Stress Response, New Target for Depression Treatment

 

http://newswise.com/...tsw-study-shows

 

 

I'm sorry if this has been mentioned here, but there's a drug already available, which acts on exactly these pathways. It's called tofisopam.

 

Tofisopam is a member of the 2,3-benzodiazepine compound family which is marketed for the treatment of anxiety in some European countries. In contrast to classical 1,4-benzodiazepines, the compound does not bind to the benzodiazepine binding site of the γ-aminobutyric acid receptor and its psychopharmacological profile differs from such compounds. In addition to anxiolytic properties, antipsychotic effects are reported [...]
We further show that tofisopam acts as an isoenzyme-selective inhibitor of phosphodiesterases (PDEs) with highest affinity to PDE-4A1 (0.42 μM) followed by PDE-10A1 (0.92 μM), PDE-3 (1.98 μM) and PDE-2A3 (2.11 μM).

→ source (external link)

 

I ordered some. 

[Flex]

 

tipepidine seems interesting so who sells it? What I find ridiculous is methamphetamine always gets compared to with a hint that it is a bad drug, when if anything it's really the ultimate stimulant. Addictive yes, but there's a reason why it's the poster child in being "compared" or "likened" to some new unproven drug no one has ever heard of. I'm on an amphetamine called Vyvanse for ADHD and boy do I wish I was on meth (Desoxyn). I'd probably achieve more in 10 years that I ever would in 30-50 years. Life is short not to live it to the fullest.

 

 

 

My opinion is that there might be a chance that You would experience detrimental effects on cognition, so that the performace curve would become more flat then proportional

Wouldnt obviously guarantee that thou

 

Seems that this is a common mechanism of Antidepressants:

 

Atomoxetine has been found to inhibit both brain and cardiac G protein-coupled inwardly-rectifying potassium channels, a characteristic it shares with the related drug reboxetine.[25]

https://en.wikipedia...iki/Atomoxetine

 

In oocytes injected with mRNA for GIRK1/GIRK2 or GIRK1/GIRK4 subunits, extracellular application of sertraline, duloxetine, and amoxapine effectively reduced GIRK currents,

whereas nefazodone, venlafaxine, mianserin, and mirtazapine weakly inhibited GIRK currents even at toxic levels.

The inhibitory effects were concentration-dependent, with various degrees of potency and effectiveness

Inhibition of G protein-activated inwardly rectifying K+ channels by different classes of antidepressants.

https://www.ncbi.nlm...pubmed/22164246

Here, we report the inhibitory effects of various antidepressants:

imipramine, desipramine, amitriptyline, nortriptyline, clomipramine, maprotiline, and citalopram, on GIRK channels.

In Xenopus oocytes injected with mRNAs for GIRK1/GIRK2, GIRK2 or GIRK1/GIRK4 subunits, the various antidepressants tested, except fluvoxamine, zimelidine, and bupropion,

reversibly reduced inward currents through the basal GIRK activity at micromolar concentrations.

Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs.

https://www.ncbi.nlm...pubmed/15150531

[bbminded]

Just to touch on Orexin.... It used to be offered by a couple research companies at the same time Selank came out. It was actually recommend to combine both in research situations.

It was actually very effective(atleast in my studies), but for some reason was dropped by the vendors, but still available was selank.
I think maybe there wasn't enough interest. Not sure but would really like to see it offered again, or if not, at least a reason why it isn't available.

[eon]

Request it from the vendor that was selling it?

 

Just to touch on Orexin.... It used to be offered by a couple research companies at the same time Selank came out. It was actually recommend to combine both in research situations.

It was actually very effective(atleast in my studies), but for some reason was dropped by the vendors, but still available was selank.
I think maybe there wasn't enough interest. Not sure but would really like to see it offered again, or if not, at least a reason why it isn't available.

 

[eon]

Since you're in Europe and tofisopam is only marketed in Europe (?), where and how did you get yours? Did it require a prescription? Is it OTC like nootropics or what?

 

 

Manipulating Molecule in the Brain Improves Stress Response, New Target for Depression Treatment

 

http://newswise.com/...tsw-study-shows

 

 

I'm sorry if this has been mentioned here, but there's a drug already available, which acts on exactly these pathways. It's called tofisopam.

 

Tofisopam is a member of the 2,3-benzodiazepine compound family which is marketed for the treatment of anxiety in some European countries. In contrast to classical 1,4-benzodiazepines, the compound does not bind to the benzodiazepine binding site of the γ-aminobutyric acid receptor and its psychopharmacological profile differs from such compounds. In addition to anxiolytic properties, antipsychotic effects are reported [...]
We further show that tofisopam acts as an isoenzyme-selective inhibitor of phosphodiesterases (PDEs) with highest affinity to PDE-4A1 (0.42 μM) followed by PDE-10A1 (0.92 μM), PDE-3 (1.98 μM) and PDE-2A3 (2.11 μM).

→ source (external link)

 

I ordered some. 

 

 

[Shai Hulud]

@eon: No, it requires a prescription and isn't even marketed in my country. I found a source that send's genuine products without prescription...at least it's supposed to be genuine and I read positive reviews about the source. Since I'm not sure if sourcing is legit on longecity, I'll send you a pm.

[bbminded]

Request it from the vendor that was selling it?

Just to touch on Orexin.... It used to be offered by a couple research companies at the same time Selank came out. It was actually recommend to combine both in research situations.

It was actually very effective(atleast in my studies), but for some reason was dropped by the vendors, but still available was selank.
I think maybe there wasn't enough interest. Not sure but would really like to see it offered again, or if not, at least a reason why it isn't available.

I think I had tried, but it was either a lack of interest from potential customers to make it worth it for the vendor to continue to carry. Or the chem just became to difficult to obtain for whatever reasons....its been over 2+ years since, so hard to remember exactly.

[Mr.No]

If your depression doesn't have serious biological background ( http://alphachoices....orsNewDrugs.pdf.  ) then i suggest to follow this program:

 

http://cdn.preterhum...ion Therapy.pdf. 

 

Its something like  healthy living (exercise, healthy eating habits etc...) vs. supplements 

[jefferson]

http://www.datamonit...ression-armory/ is a look at 5 new approaches for treating depression with drugs in clinical trials. I'm glad to see a renewed focus on the opiodergic system. It's long overdue.

[eon]

wouldn't Kratom be the best and natural opioidergic available? As far as legal goes. I think opium/poppy would be just as good if it were legal?

 

http://www.datamonit...ression-armory/ is a look at 5 new approaches for treating depression with drugs in clinical trials. I'm glad to see a renewed focus on the opiodergic system. It's long overdue.

 

Edited by eon, 19 August 2015 - 06:10 AM.

[jefferson]

The problem with Kratom is that because it strictly agonizes the mu opioid receptor, tolerance inevitably follows, and I think we know where that all too often leads. What makes the other approaches more promising is that they may not induce tolerance, making longterm use more viable.

Edited by jefferson, 19 August 2015 - 11:35 AM.

[fntms]

And also kratom has been shown to be cardiotoxic.