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Recreational drugs with silicon in their molecule

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SpiralusSancti

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Apparently from research so far it seems that certain drugs might be better/safer/have less side effects in a “silicon version”, at least it seems so in vitro, if I remember correctly from a research I read that includes haldol remake. Most drugs in that paper were not about drugs that have effects on the brain but one other beside haldol that has was example of some 5HT2a atagonist becoming agonist in a “silicon version” and makes me think there’s huge potential, maybe even for whole knew classes of drugs or lone gems with maybe really unique effects.

I guess only reason we wont see any silicon RC’s anytime soon is complex and pricey synthesis?
 
Anyone feel free to move it to N&P.

Actually haldol was found to be superior to regular version in some ways but some other substance turned out to become agonist instead antagonist but I don't remember what exactly, shouldn't be too hard to find though given there's still not a lot of research in that direction but I'm sure if it shows worthwhile that many problems concerning making that kind of molecules will be circumvented with time.
 
Hey guys!

I'm in agreement that this is definitely material for those nerds over in Neuroscience. I read the title of this thread and was instantly intrigued, as I had literally no idea how or what this would even mean. Movin' it on over to Neuroscience and Pharmacology!
 
Sort of analogous to the idea of silicon based life? Silicon replacing carbon? Yeah that's groovy man. Interesting idea.

I don't know anything beyond that.

Have been intrigued by silicon as a nutrient. Apparently extra prevalent in beer.
 
Yes, a lot like like that. But not exactly replacing every carbon atom with silicon (and purely Si based drugs would be work up from start and totally new because of difference in bonding of carbon and silicon) but some group, side chain or something is one approach that’s being used. 1silyl-LSD anyone? Well that one would be just chemistry practice in terms of working out synth & stability.
 

Science | AAAS

www.science.org www.science.org

As Derek Lowe points out - it always seems to be the second best option...

Science | AAAS

www.science.org www.science.org

And it would appear that synthesis is a pain - likely because silicon isn't much used.

For my own part, the alcohol mimic worked with an 8 ethynyl and and 8-trimethylsilyl but the problem is knowing what unusual toxicity to look out for. So we went with the safer, synthetically firmer alternative. A bit of a chicken and egg situation IMO.
 
I still believe that given enough time we’ll have new psychoactive drugs with silicon and who knows maybe even with silicon as main element. And given even more time and will some might prove really worth pursuing.
 
It's not like people haven't been trying for a long time. But it's somewhat telling that it's been most valuable in making toxic compounds - pesticides and so on.

So unless you can point to an advantage that makes it worth the extra toxicity tests, I do not see it happening. It's a metalloid and as a group, they ALL display significant toxicity.
 
Well if there are scientist that consider silicon based version of haldol might be superior and LESS toxic if that turns out correct in vivo there are certainly more examples like that. In that research with over a dozen of chemicals they found problematic that some compounds they have made are very unstable and another problem was how hard and uneconomical synthesise is.
 
Well a reference would be appreciated. I did provide some references to the problems, but I see none saying it's SAFER. Different, yes, but I do not read safer anywhere - looks more like someone is taking an established medicine and dropping an Si into it to get a patent.
 
I'm not able to link it right away but as soon I'm, will so!

Well at least one I found didn’t strike me as bs or even as if it’s main idea is to circumvent patents or something (maybe will on next reading because new info). But even if psychoactive silicon medicine wont prove out to be a winner in any kind, some other group of medicine will, well if nothing added toxicity in case of cancer medicine is good (if it doesn’t change ratio of toxicity to healthy vs. cancer tissue).

P.S. Just to be clear I didn’t mean to sound like you are not a scientist and what you posted is invalid. As I wrote scientist, not "research paper I read".
 
Imo, one the biggest problem with silicon is that silanes ie compounds with Si-H bonds are not very stable. Silicon-hydrogen bond (Si-H) is not stable compared to carbon-hydrogen (C-H). Gets easily oxidized. Isnt it why silanes are used in all sort of reductions in Ochem? So if you can’t get Si-H groups in your molecule, you pretty much exclude 99% of possible drugs that can be made. But some quaternary silicon compounds (Si atom substituted with all carbons) may be ok but even that only with relatively big C groups. I think that is the biggest issues with Silicon-containing drugs. thats just an opinion I may be wrong.
 
Organosilicon isosteres of CP-47,497 were patented some 40 years ago.

Trialkylsilicon-containing phenylcycloalkane analgesics
Patent US4379783
Publication date: 1983-04-12

You just need a drug with a quaternary carbon atom in the molecule.

Edit: Paracelsius was quicker to note the same thing :)
 
Last edited:
Hiroshi Fukasawa, Hideaki Muratake, Ai Ito, Hideyuki Suzuki, Yohei Amano, Marina Nagae, Kiyoshi Sugiyama, and Koichi Shudo
Silicon-Containing GABA Derivatives, Silagaba Compounds, as Orally Effective Agents for Treating Neuropathic Pain without Central-Nervous-System-Related Side Effects
ACS Chem. Neurosci., 2014, 5(7), 525–532.
https://doi.org/10.1021/cn500053d (free access)
Abstract
Neuropathic pain is a chronic condition resulting from neuronal damage. Pregabalin, the (S)-isomer of 3-isobutyl-γ-aminobutyric acid (GABA), is widely used to treat neuropathic pain, despite the occurrence of central nervous system (CNS)-related side effects such as dizziness and somnolence. Here we describe the pharmacology of novel GABA derivatives containing silicon–carbon bonds, silagaba compounds. Silagaba131, 132, and 161 showed pregabalin-like analgesic activities in animal models of neuropathic pain, but in contrast to pregabalin they did not impair neuromuscular coordination in rotarod tests. Pharmacokinetic studies showed that brain exposure to silagaba compounds was lower than that to pregabalin. Surprisingly, despite their potent analgesic action in vivo, silagaba compounds showed only weak binding to α2-δ protein. These compounds may be useful to study mechanisms of neuropathic pain. Our results also indicate that silagaba132 and 161 are candidates for orally effective treatment of neuropathic pain without CNS-related side effects.
Click to expand...
 
SpiralusSancti said:
I'm not able to link it right away but as soon I'm, will so!

Well at least one I found didn’t strike me as bs or even as if it’s main idea is to circumvent patents or something (maybe will on next reading because new info). But even if psychoactive silicon medicine wont prove out to be a winner in any kind, some other group of medicine will, well if nothing added toxicity in case of cancer medicine is good (if it doesn’t change ratio of toxicity to healthy vs. cancer tissue).

P.S. Just to be clear I didn’t mean to sound like you are not a scientist and what you posted is invalid. As I wrote scientist, not "research paper I read".
Click to expand...

That's a very circumscribed class. Chemotherapy is more to do with the fractionation that the (usually very toxic) agents. Said agents are used for decades because it's perfecting the use rather than the agent that is key.
 
pharmakos said:
How about a 2C with a silicon loaded with fluorines in the 4-position?
Click to expand...
With a -SiF3 group? It's impossible. Aryltrifluorosilanes are quickly hydrolyzed in the presence of water. 2C-(SiMe2F) may turn out to be sufficiently stable. However, the group is large, so the molecule is unlikely to activate 5-HT2A receptors.

H. J. Emeléus and C. J. Wilkins
Some new ethyl and phenyl silicon fluorides
J. Chem. Soc., 1944, 454-456.
https://doi.org/10.1039/JR9440000454 (paywalled)
https://sci-hub.se/10.1039/JR9440000454 (kindly pirated)
Phenyltrifluorosilane is a colourless, inflammable liquid (d174 1.212) with a pungent and aggressive smell. It is quickly hydrolysed by water and alkalis, and in the air the smell of the compound soon gives way to that of hydrogen fluoride.
...
The reactivity of the compounds towards hydrolysing agents falls sharply as the number of organic groups increases, the behaviour of the series being as follows:

SiEtF3 Immediately hydrolysed by water; reaction probably incomplete.
SiPhF3 Immediately hydrolysed by water; reaction incomplete.
SiEt2F2,
SiPh2F2 Very slight hydrolysis with water, but rapid decomposition with alkalis.
SiEt3F High resistance to hydrolysis; undecomposed by sodium in liquid ammonia.
SiPh3F High resistance to hydrolysis.
Click to expand...
 
realgar said:
With a -SiF3 group? It's impossible. Aryltrifluorosilanes are quickly hydrolyzed in the presence of water. 2C-(SiMe2F) may turn out to be sufficiently stable. However, the group is large, so the molecule is unlikely to activate 5-HT2A receptors.

H. J. Emeléus and C. J. Wilkins
Some new ethyl and phenyl silicon fluorides
J. Chem. Soc., 1944, 454-456.
https://doi.org/10.1039/JR9440000454 (paywalled)
https://sci-hub.se/10.1039/JR9440000454 (kindly pirated)
Click to expand...
"In the air the smell of the compound soon gives way to that of hydrogen fluoride"

That's the sort of qualitative analysis that the chemistry peer reviewed publication world is lacking in 2023 💙

Thank you
 
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