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A (somewhat) Complete List of Novel Antidepressants Undergoing Trials

S

seep

Bluelighter
Joined
Nov 28, 2008
Messages
1,347
http://www.neurotransmitter.net/newdrugs.html

I'm pretty sure some stuff is missing here. What?

We find a variety of mechanisms:

5-HT1a partial agonists
5-HT2c antagonists
5-HT3 antagonists
Melatonin receptor agonists
NAchR antagonists
NMDA antagonists (new ones, plus some ketamine teasers)
P38 kinase inhibitor
NK-1 antagonists (interesting)
CRF-1 antagonists
MILF analog
FAAH inhibitors
AMPA receptor modulator
GRII antagonists
GABA-a partial agonists (experiences?)
an enkephalinergic
a sigma receptor agonist (info on this one please!)
an mGluR agonist

Diminishing focus on monoamine reuptake inhibitors. Why? Limited efficacy? Market saturation? Consumer boredom?

Any personal experiences?
 
seep said:
Diminishing focus on monoamine reuptake inhibitors. Why? Limited efficacy? Market saturation? Consumer boredom?
Click to expand...

Cos they've run out of monoamines to inhibit reuptake of... they've gone thru every combination it seems for 5HT, DA, NA etc with every company having it's own "me too" monoamine reuptake inhibitor.

The current conscensus seems to be that depression is a loss of neurons (up to 30% of frontal cortex in depressed patients), and SSRIs etc likely work indirectly via BDNF-mediated neural regrowth.

When you think about it there's not much of a gap between the TCAs (from the 1960s) and the SSRIs of today... quite similar MOAs.

Allosteric modulators is IMO one of the smarter developments since it allows for tweaking of the bodies own endogenous-ligand signalling. There's a good review done by CHRISTOPOLOUS in Scientific American recently
 
djsim said:
Cos they've run out of monoamines to inhibit reuptake of... they've gone thru every combination it seems for 5HT, DA, NA etc with every company having it's own "me too" monoamine reuptake inhibitor.

The current conscensus seems to be that depression is a loss of neurons (up to 30% of frontal cortex in depressed patients), and SSRIs etc likely work indirectly via BDNF-mediated neural regrowth.

When you think about it there's not much of a gap between the TCAs (from the 1960s) and the SSRIs of today... quite similar MOAs.

Allosteric modulators is IMO one of the smarter developments since it allows for tweaking of the bodies own endogenous-ligand signalling. There's a good review done by CHRISTOPOLOUS in Scientific American recently
Click to expand...

I dont agree that depression is caused by loss of neurons, hence why several SSRI's have to be tried before one is found that is effective even tough they all promote neurogenesis.
It also takes a few weeks before the 5HT1A autoreceptors are downregulated, the same time it takes before the SSRI's are starting to get effective.
 
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Structural vomits

I'm having trouble finding the structures of the more interesting ones, like the ampakines, the GABA partial agonists, the enkephalinergic and the new NMDA antagonists. Anyone that knows, please share. First one here has endocannabinoid action.

URB597
200px-URB597.svg.png


TC-2216
240px-TC-2216_structure.png


SSR-125543
imgsrv.fcgi


SA-4503
200px-SA_4503.png


RX-10100
200px-Clavulanic_acid_structure.svg.png


TYRIMA
200px-CX157_structure.svg.png


CYCLOSERINE
220px-Cycloserine.png


SSR-411298
0


NEMIFITIDE
244634.gif


MECAMYLAMINE (WRONG ENANTIOMER)
150px-R-Mecamylamine.svg.png


LOSMAPIMOD
200991914330125.jpg


THE MILNACIPRAMS
300px-Milnacipran_Enantiomers_Structural_Formulae.png


SEP-225289
220px-SEP-225289_structure.png


LU AA21004
286076.gif


AGOMELANTINE
220px-Agomelatine.svg.png
 
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not all of these are for depression. The GABA partial agonists are for anxiety (obviously) read through there carefully
 
Hammilton said:
not all of these are for depression. The GABA partial agonists are for anxiety (obviously) read through there carefully
Click to expand...

Yeah.

The GABA partials, the enkephalinergic and the NMDA antagonists are mostly from the same maker, AZ, and with the exception of d-cycloserine I can't find the structures.
 
LU AA21004 has potential, possibly for social anxiety too. I just hope it isn't also an SSRI.

Agomelatine IS promising, better than any SSRI. SSRI's are ''me-to'' drugs as the previous poster mentioned.

Hey, I'm still somewhat new here. Can anyone inform me if there is a general FILES section at bluelight where I can download pdfs and such?

Just curious.

I would post the 2007 pdf I found awhile ago.
 
This is a good thread you started Seep, thanks.

I don't normally lurk at BL.ru due to BL's general obsession with getting high/messed up. I'm much more interested in neurological benefits like anxiolysis than in cognitive impairment via Cannabis, Heroin, stims, etc.

I normally stay away from BL for the reason it takes me FOREVER to find a good thread like this. THe neurotransmitter.net list could DEFINITELY be more comprehensive... especially if all the novel drugs being researched in Russia were included. Perhaps grounds for a separate improved list?

IMO the FDA is not the end-all authority in the matter what constitutes a good drug. In a way I am glad we have FDA for keeping standards high, but at the same time I see decent drugs being tucked away into the abyss due to marketing purposes (ie it costs so damn much for a drug to survive the entire FDA drug approval process). If only Americans spent a fraction of what they spend on frivolous entertainment to instead fund noble research purposes... only in my imaginary ideal world I guess.
 
Bluejay1 said:
THe neurotransmitter.net list could DEFINITELY be more comprehensive... especially if all the novel drugs being researched in Russia were included. Perhaps grounds for a separate improved list?
Click to expand...

Yes, a global list is something I want to see put together; that, and maybe getting some of the more interesting makers (Lundbeck, Sepracor, CeNeRx, Rexahn, etc) to sponsor research in my neck of the woods. Who's doing what in Russia?

Many of these compounds have been discussed on ADD before: the FAAH inhibitors, for instance, and certainly the triple RIs. Not much firsthand experience though (for obvious reasons), which makes me think some of these may actually work.

And then there's AZ's trials.

@ djsim: what are we allosterically modulating? I like the principles of minimal intervention and endogenous habilitation. Neurogenesis per se scares me.
 
obtain that list, will post 2007 version if there is a general files section

we definitely have like-minded desires.

It would be very useful for those with depression, ADD, psychosis, etc if an even-more encompassing list of substances was kept and updated.

I have little skill in the computing dept, ie i dont even have my own webpage so this is out of my scope, however, I could be one of contributors to compiling a list..

NT.net's list seems to be specific to only particular FDA drugs, so it wouldnt be polite to request the listing of international drugs.

Russians are constantly experimenting in novel drugs. ACTH fragments, vasopressin fragments, peptide analogues, you name it.. They dont have as much restrictions on their creativity as 'Western' researchers have imposed on them.

The only problem is 90% of their research is done in Russian so needs to be translated first.. I don't know Russian, otherwise I'd know a lot more about it.

I'm not saying Russian research is somehow superior, it is just rather different and commendable.

I know a handful of ppl that seem very talented at procuring Russian pdf's, however, I lack that talent and they are other forums..

If you can get the updated 2009 list of drugs in that link that would be an enormous head start on a decent list.

Anyway hope you all are having a good one. :\
 
djsim said:
The current conscensus seems to be that depression is a loss of neurons (up to 30% of frontal cortex in depressed patients), and SSRIs etc likely work indirectly via BDNF-mediated neural regrowth.
Click to expand...

Do you have a link to a journal article discussing this loss of neurons in the frontal cortex? I've heard about the neurogenesis, but from what I've read that was confined to the hippocampus.
 
Does anyone know anyone who's had RX10100? Clavulanic acid. It's scheduled in Australia. Don't think I've ever seen an aphrodesiac/antidepressant/antibiotic before.
 
Seep, have no experience with Clavulanic acid, although I've heard of it. Im a bit wary of medicinal strength aphrodesiacs it just doesn't seem natural.

got a copy of 09 pipline def worth looking at if you like research chems, however, its size exceeds the 97 bits I am allotted by BL so I can't even upload it :(
 
boohigh, I can't reply to messages yet, being that I'm still stuck in Greenlight status and it may be awhile..
 
Why no mention of opioid kappa antagonists on this list?

Im probably going out on a limb here, but I tend to believe that the instant "mood lift" that bupe provides (as opposed to the typical opioid euphoria which is absent in bupe), is more due to its antagonism at kappa then its agonist at mu.
anyone else agree?-DG
 
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