Research Project Ideas

[Dondante]

Research

I'm going to be doing research in pharmacology/biochemistry this coming summer and I'm looking for research ideas. I can pretty much do whatever I want and I have access to tons of resources. I can screen novel psychoactive compounds across a bunch of receptors. I can look at mechanisms of hallucinogen action on a molecular or cell level.

I'm going to start coming up with some general ideas, but if anyone has input, I'd love to hear it.

Thanks!

 

[Jamshyd]

People who research the role of NMDA-antagonists in depression and anxiety are really, really, cool .

Its the newest In-thing, you know? Slightly risque though, since the word "phencyclidine" tends to cause spontaneous research-paper-ethnic-cleansing... try to avoid this one. There are several others.

Just a thought.

 

[Dondante]

I actually contacted someone who does brain imaging studies that involve the cortico-limbic network and NDMA antagonism, but she hasn't gotten back to me. This lab isn't giving ketamine as a therapeutic, but it's still interesting research.

I guess I shouldn't say that I'm definitely working in the pharmacology/ biochem lab, but the opportunity is there, so I can't see why I wouldn't. This lab deals mainly with 5-HT2A, and also only with cell cultures and mice.

 

[Enlitx]

I also work in a biochemistry lab, I am currently studying the role of acetylcholine esterase in plant signaling. Later when I write a proposal for some university funding I might expand my scope to include other neurotransmitters, including GABA and glutamic acid, which have both been indicated to exist at a small concentration in the tobacco plant I am working with. Its interesting to analyze the role of neurotransmitters in plant signaling, only a handful of publications deal with the topic at any length. Hopefully that means that my data will be worthy of publication.

I know you probably want to deal with topics relating to the human brain, but I thought I might throw that out there. It is a lot easier to get published in this relatively unknown field.

 

[Dondante]

Well, assuming I work in the lab mentioned, work will be either on human or mouse CNS receptors + any psychoactive compounds (preferrable ones that interact with the king of all receptors ... 5-HT2A. Thanks for the input though.

 

[Pharaoh Sphinx]

do something on sigma receptors, theyre mad cool

 

[vecktor]

Well, assuming I work in the lab mentioned, work will be either on human or mouse CNS receptors + any psychoactive compounds (preferrable ones that interact with the king of all receptors ... 5-HT2A. Thanks for the input though.

I personally would like to see receptor affinity studies for 4-alkylamino tetrahydro benz(cd)indoles. they were discovered and researched before the discovery of 5ht2a and other receptor subtypes and long before cloned receptors. they are known to be dopaminergic agonists and there is some contradictory evidence that they are also serotonin agonists probably at 5ht1, I would love to see some modern data. thay are the link between the clavines the ergolines and the simple tryptamines.

the dmt benz(cd)indole is below cut and paste the smiles into a molecular viewer,
smiles:
N([C@H]3CC2=C1C(=C[N](C1=CC=C2)[H])C3)(C)C

V

 

[mad_scientist]

I'm sure the community would be interested in any new 5HT2A agonists you can devise

Inventing and characterising some novel 2C's would be interesting and not too complicated from a synthetic standpoint if you have the resources...compounds like 4-perfluoroethyl-2,5-diMeO-PEA, 3,4-bis(trifluoromethyl)-2,5-diMeO-PEA, 4-pentafluorosulfonyl-2,5-diMeO-PEA have never been made and might be interesting with all that electronegativity at the 4-position.

Or for something more challenging go more complicated and try unravel the molecular signalling pathways inside the cell that get activated when an agonist binds to 5HT2A, research into the regulators of G-protein signalling (RGS) proteins was big when i was at uni, and it would be interesting to develop small-molecule drugs which affected those, could potentially come up with a hallucinogen that acts further downstream than normal 5HT2A agonists like LSD, and hence would be entirely structurally distinct.

 

[Dondante]

Thanks for the input guys! Here's a few initial brainstorm ideas I've come up with.

Look at the mechanism and/or importance of PLD activation by the 5-HT2A receptor. See if it is G13 mediated as in the 5-HT2C receptor. This is probably more of a thesis project rather than a summer one.

Confirm that hallucinogenic phenethylamines are indeed agonists of the human 5-HT2A receptor, since it has been shown that they are antagonists for rat 5-HT2A receptors in xenopus laevis oocytes. This would be very easy, but ultimately fairly pointless.

It would be interesting to explore downstream activity such as glutamate function/ alteration in response to psychedelics.

Screening some novel compounds would be interesting too and not too difficult.

 

[Jamshyd]

I would die to see anything about the following, concerning 5HT:

1. PiPT! (N-propyl,N-isopropyltryptamine).

2. An investigation of the auditory effects of DiPT.

3. More research to support the safety of DPT and 2C-D since I agree with dr. Grof and many others that they, along with LSD, make superb psychotherapeutic agents.

I know this stuff is VERY basic, but I think at our present stage it would probably be much more usefull than looking at tiny details that just serve to generate more questions. I don't mean to demean your suggestions, I just think some more basic stuff ought to be established before delving into the nitty-gritty.

 

[Dondante]

Does anyone know of any proposed mechanisms for the unique effect of DIPT? I doubt there's another receptor involved, so what could cause it to have this effect that is lacking in all similar tryptamines?

Ibogaine and analogs could be interesting. I don't think there are any comprehensive studies on the receptor profiles of these compounds.

Edit: maybe I was wrong about this

Development of novel medications for drug addiction. The legacy of an African shrub.Glick SD, Maisonneuve IM.
Department of Pharmacology and Neuroscience, Albany Medical College, New York 12208, USA. [email protected]

Ibogaine and its metabolite noribogaine have low microM affinities for kappa and mu opioid receptors, NMDA receptors, 5HT-3 receptors, sigma-2 sites, sodium channels and the serotonin transporter. 18-MC has low microM affinities at all three opioid receptors and at 5HT-3 receptors but much lower or no affinities for NMDA and sigma-2 receptors, sodium channels, and the 5HT transporter.

Are there any other plants with relatively unexplored psychoactive compounds? Kratom?

 

[fastandbulbous]

Are there any other plants with relatively unexplored psychoactive compounds? Kratom?

Can't remember the species, but the active alkaloid is bulbnocapnine. Years ago at uni I remember reading something about it being a psychedelic that induced a state not unlike paralysis - to me that sound like an NMDA antagonist, but there's bog all info on the drug; most web sources just seem to repeat the little that is known

 

[kidamnesiac]

Are there any other plants with relatively unexplored psychoactive compounds? Kratom?

Peyote...
I read a recent paper saying several new salvinorin analogs have been extracted in trace amounts from the plant, if you're working with the kappa receptor, well, bingo

http://scholar.google.com/url?sa=U&q=http://www.sagewisdom.org/salvinorind-f.pdf

http://scholar.google.com/url?sa=U&...ract.cgi/orlef7/2005/7/i14/abs/ol0510522.html

(gotta have JACS access)

has the biosynthetic pathway for the salvinorins been elucidated? It would be surprising if it has not as the synthesis has escaped several organic chemists since 1982, which is quite a long time. with an interest in enzyme engineering, methinks these enzymes must have some interesting chemistry going on

 

[vecktor]

Can't remember the species, but the active alkaloid is bulbnocapnine. Years ago at uni I remember reading something about it being a psychedelic that induced a state not unlike paralysis - to me that sound like an NMDA antagonist, but there's bog all info on the drug; most web sources just seem to repeat the little that is known

this is a south african herb, can't remember the name, very toxic and has been implicated in quite a few deaths.
the genus is amaryllidaceae and the afrikaans name for these bulbs is gifbal = poison ball doesn't sound too pleasant.
a quick search indicated that they mostly contain alkaloids from the indolizidine family which links then into the loco weed alkaloids from erythrina species

edit
a bit of research later..the whole thing can be summarised in two words --- toxic deleriant.

 

[fastandbulbous]

has the biosynthetic pathway for the salvinorins been elucidated? It would be surprising if it has not as the synthesis has escaped several organic chemists since 1982, which is quite a long time.

Didn't think that the structure of salvinorin A had been resolved back in '82 (thought that happened a lot later)

 

[kidamnesiac]

84, sorry

Divinorin A, a psychotropic terpenoid, and divinorin B from the hallucinogenic Mexican mint, Salvia divinorum

Journal of organic chemistry [0022-3263] Valdes III yr:1984 vol:49 iss:24 pg:4716


even got a xtal structure in there i think

 

[nuke]

I would like to see information in regard to the human metabolism of 2c-t-x compounds, and 2,3,5, 2,3,6 and 2,4,6 phenethylamine compound binding affinities.

 

[BilZ0r]

What techniques do you have access to? I mean, while doing Oocyte recording in a lab that has oocytes already stripped and inject with cDNA already made up, and has a TEVC system already set up; yeah, that's easy. But if you want to work that system from the ground up; it's going to take you a fuck load longer than just a summer.

So what do the labs you might be able to work in have? Ligand binding? Electrophysiology? Behavioral Pharmacology? Immunohistochemistry? Enzyme activity? etc...

 

[Dondante]

The lab does ligand-binding, GPCR activation (also G protein, effector, second messenger, and transcriptional activation) receptor internalization and/or desensitization.

No behavioral pharmacology, no electrophysiology. I think yes for immunohistochemistry and enzyme activity. I sent you a PM.

 

[Dondante]

Can't remember the species, but the active alkaloid is bulbnocapnine. Years ago at uni I remember reading something about it being a psychedelic that induced a state not unlike paralysis - to me that sound like an NMDA antagonist, but there's bog all info on the drug; most web sources just seem to repeat the little that is known

Maybe I'll check it out ... sent a PM.