Seratonin Analogues etc...? Synthetic Neurotransmitters?

[Choronzon333]

I read Alexander Shulgin's Tihkal and Pihkal a couple of years ago. While the substance descriptions are interesting, reading the actually book shed alot of light on a lot of interesting areas. One thing that really caught my mind was his story about how he became interested in Psychopharmacology and the process that led him to creating 100's of tools to probe the mind with. I'm talking about Research chemicals of course.

Anyway, reading how he started, he said he basically started with mescaline and some of the few known tryptamines(this was back in the 50's) and started playing with molecules. From mescaline he built many many phenephalamines including much of the 2cx family. He has also brought about many tryptamines based on various indoles and alkalines.

One thing that occured to me that I haven't gotten to talk about much, is what other starting points one could use for developing interesting chemicals that interact with the brain to provide unique insight into the workings of the psyche as well as the psychological brain. Has anyone ever tried or thought about trying to start with serotonin and modifying it like shulgin did with mescaline in order to create an array of new substances? It seems like since serotonin is active, close chemicals(closer than the usual other tryptamines) Could produce very interesting effects. Perhaps someday a neurotransmitter superior to serotonin could be discovered and by supplementing our brains with it we could gain post human abilities. Its a far off and weird thought but curious none the less.

Have there been attempts to develop or development or even talk of psychedelic or nootropic substances that even more closely resemble serotonin? I am interested to hear because everyone here seems to know alot about chemistry and the state of psychopharmacology today. I'm not talkin natural supplements or precursors like 5htp, I mean bonafide synthetic serotonin analogues and the like.

 

[dread]

alpha,o-dimethylserotonin comes to mind.

 

[Choronzon333]

alpha,o-dimethylserotonin comes to mind.

whats that?

 

[dread]

It's serotonin with 2 methyl groups added to it.

 

[ungelesene_bettlek]

It seems like since serotonin is active, close chemicals(closer than the usual other tryptamines) Could produce very interesting effects.

"usual tryptamines" are already very close to serotonin (in fact, serotonin is 5-hydroxy-tryptamine).

alpha,o-dimethylserotonin is better known as 5-MeO-AMT, btw.

 

[dread]

And btw, care to give a reason as to why would something be more active just because it's closer to serotonin? This has always baffled me.

Psilocin is probably the closest thing to serotonin (add 2 n-methyls, move the hydroxyl 1 carbon to the right) and yet, LSD which is nowhere near serotonin is many many times more potent by weight.

 

[Mjäll]

I am intrigued by the idea byt I do not have the chemical expertise to enlighten any further. It would seem, though, that Shulgin himself would have tried other interesting options if there were any.

But it's strange how most of the psychedelic substances are structurally very similar. To my knowledge, this is not true for stimulants, for example, or depressants, which may have entirely different structures, and still manipulate the brain in similar ways. Am I correct?

 

[dread]

But it's strange how most of the psychedelic substances are structurally very similar. To my knowledge, this is not true for stimulants, for example, or depressants, which may have entirely different structures, and still manipulate the brain in similar ways. Am I correct?

Not exactly. Each of these classes have their own SAR. Most of the psychedelics are either tryptamines, phenethylamines or ergolines. Most of the stimulants are phenethylamines or tropanes, although there are more than a few odd birds there. But, psychedelics have their odd birds as well. As for depressants, there are so many things you could call depressants, that it becomes irrelevant...

 

[Choronzon333]

And btw, care to give a reason as to why would something be more active just because it's closer to serotonin? This has always baffled me.

Psilocin is probably the closest thing to serotonin (add 2 n-methyls, move the hydroxyl 1 carbon to the right) and yet, LSD which is nowhere near serotonin is many many times more potent by weight.

I never assumed it would be MORE active than other substances. You are absolutely right. Just bc serotonin is naturally in our brain does not mean it is most active. That is why I started this thread. I just assumed it would be a good starting place because since serotonin works like serotonin, maybe the right substance could function more efficiently and be a better transmitter. Perhaps without the typical psychedelic effects, that while valuable, aren't necessarily conducive to functioning "normally" while on them, it could bring about a higher level of human functioning?

I mean, think distant future. People might supplement their serotonin with the much more effective X chemical by taking x precursors or prodrugs daily. Even further, perhaps through genetic engineering people could be coded to produce it and have and X chemical system instead of serotonin system in the brain... thats kinda what i'm getting at...

Could this ever be done with current psych'S? wHAT if our brains used LSD in a transmittor like way instead of now where it agonizes and excites an unusual reaction in the brain. I'm not a neurologist so I'm sorry if it sounds far fetched or is impossible for a reason I don't understand. Just an interesting thought I had.

 

[Choronzon333]

I am intrigued by the idea byt I do not have the chemical expertise to enlighten any further. It would seem, though, that Shulgin himself would have tried other interesting options if there were any.

But it's strange how most of the psychedelic substances are structurally very similar. To my knowledge, this is not true for stimulants, for example, or depressants, which may have entirely different structures, and still manipulate the brain in similar ways. Am I correct?

To an extent. Stimulants work in several different ways thoughs, on different systems. Alot are very similar structurally and in mode of action. Cocaine and meth and other amphetamines are all dopamine reuptake inhibitors. The amphetamines can also be dopamine releasing agents. THere are lots of amphetamines or chemicals closely related that work the same or similar ways. Because amphetamines(like amphetamine, meth, benzedrine... not broader category) are a type of phenephlyamine they are also structurally similar to many psychedelics and entactogens. Some drugs have action on dopamine systems as well as seretonin. I believe MDA and MDMA to some extent would be an example? MDA can also have psychedelic effects making a very interesting substance.

 

[Putingrad]

You're certainly going out on an interesting conceptual limb here, but the premise of "super-neurotransmitters" is fatally flawed, in that the chemical systems and their receptors of our body are linked utterly to their corresponding endogenous neurotransmitters. It would not be a matter of constructing a compound that would most efficiently double as a certain transmitter, but of constructing a person or people to possess neurochemical systems capable of utilizing this compound.

Sci-fi territory, to be sure.

Also, as dread mentioned, many of the tryptamines are about as close as you can get to serotonin yet they don't function as serotonin,instead activating the system in atypical ways.

 

[Choronzon333]

You're certainly going out on an interesting conceptual limb here, but the premise of "super-neurotransmitters" is fatally flawed, in that the chemical systems and their receptors of our body are linked utterly to their corresponding endogenous neurotransmitters. It would not be a matter of constructing a compound that would most efficiently double as a certain transmitter, but of constructing a person or people to possess neurochemical systems capable of utilizing this compound.

Sci-fi territory, to be sure.

Also, as dread mentioned, many of the tryptamines are about as close as you can get to serotonin yet they don't function as serotonin,instead activating the system in atypical ways.

I know. That is what i'm getting at. I was wondering if ppl had found or could find compounds the activate the serotonin system in a more typical way like serotonin itself rather than overstimulating and causing atypical effects. That would be the first step. Perhaps it isn't possible though with our current DNA Like you said, that's why I think it be interesting to see in the coming century or two or 3 if the brain could be redesigned genetically to perform using different more efficient transmitters from birth say...

I don't know if that could work with current compounds and am not a chemist admittedly but perhaps with the right compound it could work eventually?

 

[egor]

I did a few trials with bufotenin (5-ho-dmt) via yopo and cohoba snuffs and extracts and I just dont see the 5-ho tryptamines going anywhere worthwhile. Just look into alphamethylseritonin (5-ho-amt) if you want an idea of what to expect...

 

[ShaolinBomber]

You would have to restructure the human DNA to actually produce (the neurotransmitter) and respond (receptor for said transmitter) for your idea to even be concievable. Such a science is way way off IF its even managable at all. The closest they are right now is epigenetics and using this new discovery to restructure soft coding. However, hard coding new genetic information is next to impossible given our current understanding of Biology.

Psychedelics and such work because they are serotonin receptor AGONISTS, meaning they will compete with serotonin for the receptor spot.

 

[Solipsis]

You can take synthetic GABA, that does produce an effect for me...
Phenibut is a nice GABA derivative thats very nice.

I'd be interested to hear what other analogues there are although I start to get more and more worried about fucking up your whole GABA system with all these agonists.

None of this is psychedelic of course

 

[Choronzon333]

You would have to restructure the human DNA to actually produce (the neurotransmitter) and respond (receptor for said transmitter) for your idea to even be concievable. Such a science is way way off IF its even managable at all. The closest they are right now is epigenetics and using this new discovery to restructure soft coding. However, hard coding new genetic information is next to impossible given our current understanding of Biology.

Psychedelics and such work because they are serotonin receptor AGONISTS, meaning they will compete with serotonin for the receptor spot.

Ok. SO you would most certainly have to go about DNA recoding. That makes sense. I was talking any point of the future. As you might note I said in a previous post for the DNA recoding that the timeframe could be anywhere in the next 300 years.

 

[hybridweb]

Yo! I found this thread and thought it was interesting, thought I'd follow up even though it's a year and a half later. I noticed a problem with the idea of creating a serotonin analogue that acts more efficiently than serotonin does, though, if you were to try to use this as a replacement neurotransmitter. Essentially, the problem is that more does not equal better. One of the reasons that neurons have reuptake mechanisms is so that the pre-synaptic neuron can modulate the strength of the signal that it transmits. The whole brain is built in such a way that it sends very precisely controlled signals within itself. If, for example, neurons in the serotonin system have reuptake mechanisms that work to efficiently, the pre-synaptic neurons send weaker signals than they should. This is one potential cause of depression, and this is why SSRIs work to treat depression. By blocking some of the reuptake, you allow the pre-synaptic neurons to transmit a stronger signal, resulting in better regulation of mood. I'm pretty sure that if your pre-synaptic neurons were to send signals that were too strong, this could lead to a whole host of problems from the over-stimulation of the post-synaptic neurons. For example, I know that SSRIs can trigger a manic episode in some people with bipolar disorder (which is interesting, since I believe that bipolar disorder is actually correlated with low levels of serotonin, but that's another story). Signals sent using serotonin need to be finely modulated because serotonin may also act as a neuroregulator, regulating the behavior of other neurotransmitter systems. This means that a malfunction in the serotonin system could lead to malfunctions in many other systems throughout the brain.
That's why I think replacing serotonin with a more efficient analogue neurotransmitter would be a bad idea - the brain is finely tuned, so a stronger signal does not equal better mental functioning. However, it can be much more interesting in the short term, so we should probably all rock the occasional MDMA.
As a quick analogy I just thought of, a stronger neurotransmitter signal is like putting NOS in your car engine - really fun and fast for a short time, but if you try to run your car on NOS for too long, you'll tear the engine to shreds.
Anyway! That's my forty-two cents. Sorry if any of the information on the neurotransmitter system is wrong, I'm an undergrad psych student and still learning.

Peace!

 

[Kindness123]

N,N-Dimethylserotonin. I know this thread is really old but it doesn't seem like anyone mentioned what in my opinion is the most obvious choice for a serotonin analogue, N,N-Dimethylserotonin. More commonly known as Bufotenin, or 5-Hydroxy-DMT. But I'd like to point out to you that the "DM" in 5-HO-DMT stands for "DiMethyl", and if you were to remove that dimethyl group, you'd be left with good ole' 5-Hydroxytryptamine, more commonly known as our good friend Serotonin! Which means that bufotenin is N,N-Dimethylserotonin. If you've read many Tihkal/Pihkal entries you know that the chemical names of molecules can be rearranged to however suites your fancy. Here's the Tihkal entry for Bufotenin, in which one name he gives it is actually N,N-Dimethylserotonin. Even Sasha knew of the molecule's nature.

https://www.erowid.org/library/books_online/tihkal/tihkal19.shtml

I think 5-Ho-DMT is fascinating case of a molecule because not only is it one of the closest known relatives to serotonin, but it's also about as close as you can get to DMT (besides Mushrooms of course, the active molecule being psilocin; 4-HO-DMT). And considering that Serotonin and DMT are two of the most primary active neurotransmitters in the human brain, this puts Bufotenin in the position of being some rare chance of insight into the inner workings of the human mind.
It's unfortunate that 5-HO-DMT is so rare to come by, even on the online markets. Especially since I would want to try the good stuff synthesized specially by the sacred chemist of a frog.

 

[Nexus_Tripper]

5-HO-aMT and 5-HO-aMT are as close as you're gonna get.

 

[Solipsis]

You cannot confine a drug to the brain, and drugs too similar to serotonin are likely to have too many peripheral effects - cause serotonin is the ligand for all serotonin receptor subtypes and you don't want to flip em all on indiscriminately.