could this obscure drug be a potent nootropic... (riluzole)

[asecin]

i have never even heard of this one until yesterday by browsing wikipedia as i do randomly and i see this page; http://en.wikipedia.org/wiki/Riluzole
it says, its specifically designed for one disease and that is some serious one called amyotrophic lateral sclerosis aka ALS, AND it actually benefits such people to extended time. that is some serious disease and that is some seriously in mind designed drug to try to pick on that specifically.
so anyway, i go on as i do, reading more about it. the way it works, it seems to be a potent nootropic. i said, well wikipedia is not reliable source lets read more of it on ncbi, and what do i get? some interesting articles on its potent BDNF activity, comparison to resveratrol, anticonvulsant, anxyolytic, against dementia and many on being a potent antidepressant with few articles popping up with ketamine close second. BUT, it seems to have been studied predominantly for ALS therefore ignoring many other possible benefits!
what do you guys think? good potent obscure nootropic that doesnt have any serious side effect to speak of?

 

[sekio]

good potent obscure nootropic that doesnt have any serious side effect to speak of?

... and doesn't afraid of anything? (sic) I think "doesn't have any serious side effects" is going a little far. "Well tolerated in most", sure. But eventually there's going to be a few people who will get horrible adverse reactions just like any other drug out there.

It seems there's actually a fair bit of research on riluzole's usage for other things (as you note from PubMed searches). I think a part of the issue is that the FDA is really reticent to tack on new prescribing indications for drugs so a lot of doctors (who are generally busy treating patients instead of reading literature on every drug possible) aren't aware of their potential usage.

A lot of small molecule drugs that are "specifically designed" for one usage are not really so much "designed" as "selected"... a good example is - there was a company recently screening drugs to encourage pancreatic beta cells to grow, one of the major lead chemicals that had activity they found was harmine, the popular MAOI... it just goes to show that little molecules tend to fit into LOTS of places!

This is a good find, it definitely looks like a drug that has promise in a lot of areas. It seems quite expensive compared to a lot of other drugs though.

 

[checktest]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681895/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424768/

Does seem like an interesting drug. Pretty decent amount of protective qualities for a single compound, though the incidence of physical effects is something to consider in other uses.

I thought there was a research that was just monotherapy with riluzole at MGH, but it looks like there is instead one with it as an add-on to an SSRI for depression. Interesting to see how it would go with more stimulating compounds, in terms of limiting glutamate release.

And speaking of screened MAOI compounds as funny ligands:

http://www.ncbi.nlm.nih.gov/m/pubmed/21885739/

Tranylcypromine was quite a NET ligand, and Phenelzine was up there as well.

I wonder how many compounds in development will pass through a battery of structure development and be judged from that, even though plenty of drugs out there right now have pretty significant effects not originally known as part of their mechanism. Kind of comparing to an unknown.

Interesting with the Biguanides as well. But back to riluzole. I wonder how it would go with an HDAC inhibitors for memory and neuronal protection.

 

[asecin]

... and doesn't afraid of anything? (sic) I think "doesn't have any serious side effects" is going a little far. "Well tolerated in most", sure. But eventually there's going to be a few people who will get horrible adverse reactions just like any other drug out there.

It seems there's actually a fair bit of research on riluzole's usage for other things (as you note from PubMed searches). I think a part of the issue is that the FDA is really reticent to tack on new prescribing indications for drugs so a lot of doctors (who are generally busy treating patients instead of reading literature on every drug possible) aren't aware of their potential usage.

A lot of small molecule drugs that are "specifically designed" for one usage are not really so much "designed" as "selected"... a good example is - there was a company recently screening drugs to encourage pancreatic beta cells to grow, one of the major lead chemicals that had activity they found was harmine, the popular MAOI... it just goes to show that little molecules tend to fit into LOTS of places!

This is a good find, it definitely looks like a drug that has promise in a lot of areas. It seems quite expensive compared to a lot of other drugs though.

how expensive is it? i couldnt find it anywhere but then again its quite uncomfortable looking for prices on my phone.
anyway, im just interested in your opinion on some possibility of it being a good nootropic agent, even though there are quite a few areas it might be beneficial. what do you think personally on that, since you understand your biochemistry and you can judge the molecule structure?

 

[sekio]

I did some cursory looking, a generic is in the range of $300/50x60mg pill in the US, the brand name is like $3000 for the same count/dose.

I guess it's not too bad, but that's not amoxicillin-priced.

what do you think personally on that, since you understand your biochemistry and you can judge the molecule structure?

Predicting properties of small molecules as drugs is a tricky business. All I can tell you is it looks like it's an interesting compound and that there seem to be lots of potential uses for it.

 

[mister]

It did seem appealing until I got to the part where it mentions common adverse effects, one being decreased lung function >10% and less common 0.1-1% Interstitial lung disease. That's kind of off putting

 

[asecin]

wow thats really expensive! its crazy. it must be quite a new drug to be so expensive and also not very popular either. which brings me to mister, if its not popular at all and very rarely anyone ever used it, most including people with the severely debilitating disease of amyotrophic lateral sclerosis which is deadly, the actual adverse event being reported of lung problems might not be so significant for someone taking the drug not having the disease, no? that is, remember, the drug has been taking and reported it having those adverse effects specifically by the people having the disease.

from wikipedia; "ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscle wasting. This results in difficulty speaking, swallowing, and eventually breathing" the disease the drug is taken for specifically causes lung dysfunction...

 

[sekio]

I think part of the issue is drug pricing in America is artificially inflated... e.g. when insurance covers 95% of your drugs, the drug companies can raise prices a huge amount before patients actually start to complain. I believe in other countries (India) you'd see much cheaper riluzole for sale. But we don't really discuss supply here

Riluzole was introduced in the USA in 1996, so it's not that new. Obviously there has been enough of it used to get some statistics and do some studies, and but it certainly has a chicken and the egg type scenario here. If the drug was cheaper and more accessible, it would certainly be more widely used.

 

[s0rsha]

I did some cursory looking, a generic is in the range of $300/50x60mg pill in the US, the brand name is like $3000 for the same count/dose.

Those are some pretty staggering prices, but I guess that is indeed because of the differing insurance system. Riluzole in its original brand-name formulation approved in 1996 costs some $280 for 56 tablets of 50 mg in a certain Northern European country and that is the theoretical price without the default free-of-charge basic insurance that all citizens are covered by, meaning that the patient pays at most $180/56 tablets without any form of third-party insurance package. If the cost of the patient's prescription medicines exceeds $645 during the year, which it obviously would in this case, patients get the following refills for $1.60/56 tablets, essentially reducing the cost to 1 %...

As for the substance itself, it does not seem to add any real benefit when used as an add-on to ketamine therapy for treatment-resistant depression (free paper here), nor does it seem very promising in the treatment of patients with TRD who are non-responders to ketamine (free paper here). As a nootropic, who knows?