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Caine
lab rat



Registered: 01/25/10
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Peptide psychedelics?
#14411132 - 05/06/11 04:19 PM (12 years, 9 months ago) |
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So I was reading about peptide toxins, and noticed that some of them have ridiculously low LD50's. Botulinum toxin's was in the nanogram range in monkeys (1/1000th of a microgram) which is insane. I am curious to know whether or not it would be possible to (bio)synthesize some incredibly powerful 5-HT2A agonist peptides? Seems like that would be an interesting field to do some work in, if not incredibly difficult since peptides can be massive molecules...
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2Cents



Registered: 12/04/08
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Re: Peptide psychedelics? [Re: Caine]
#14411173 - 05/06/11 04:26 PM (12 years, 9 months ago) |
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....what the fuck is a peptide psychedelic?
-------------------- Long live the Shroomery!!!
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Mad_Larkin

Registered: 11/29/07
Posts: 18,606
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Re: Peptide psychedelics? [Re: Caine]
#14411180 - 05/06/11 04:28 PM (12 years, 9 months ago) |
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What's the mechanism of action for Botulinum toxin? In other words, how can it kill you at such low doses?
Cba to Wikipedia.
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Caine
lab rat



Registered: 01/25/10
Posts: 3,920
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Re: Peptide psychedelics? [Re: Mad_Larkin]
#14411187 - 05/06/11 04:29 PM (12 years, 9 months ago) |
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Paralysis, but I'n not sure what about it makes it so potent.
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Samuel L Jackson
Bad Motherfucker


Registered: 12/10/09
Posts: 8,395
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Re: Peptide psychedelics? [Re: 2Cents]
#14411189 - 05/06/11 04:29 PM (12 years, 9 months ago) |
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Quote:
2Cents said: ....what the fuck is a peptide psychedelic?
as of now, a hypothetical hallucinogenic protein.
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2Cents



Registered: 12/04/08
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Quote:
SamuelLJackson said:
Quote:
2Cents said: ....what the fuck is a peptide psychedelic?
as of now, a hypothetical hallucinogenic protein.
So it's not something yet synthesized? Any links to this hypothetical protein research or is this a lone shroomerites crazed ramblings?
-------------------- Long live the Shroomery!!!
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Mad_Larkin

Registered: 11/29/07
Posts: 18,606
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Re: Peptide psychedelics? [Re: Caine]
#14411212 - 05/06/11 04:36 PM (12 years, 9 months ago) |
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Quote:
The heavy chain of the toxin is particularly important for targeting the toxin to specific types of axon terminals. The toxin must get inside the axon terminals in order to cause paralysis. Following the attachment of the toxin heavy chain to proteins on the surface of axon terminals, the toxin can be taken into neurons by endocytosis. The light chain is able to cleave endocytotic vesicles and reach the cytoplasm. The light chain of the toxin has protease activity. The type A toxin proteolytically degrades the SNAP-25 protein, a type of SNARE protein. The SNAP-25 protein is required for vesicle fusion that releases neurotransmitters from the axon endings (in particular Acetylcholine).[58] Botulinum toxin specifically cleaves these SNAREs, and so prevents neuro-secretory vesicles from docking/fusing with the nerve synapse plasma membrane and releasing their neurotransmitters.
Though it affects the nervous system, common nerve agent treatments (namely the injection of atropine and 2-pam-chloride) will increase mortality by enhancing botulin toxin's mechanism of toxicity[citation needed]. Attacks involving botulinum toxin are distinguishable from those involving nerve agent in that NBC detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when a sample of the agent is tested. Furthermore, botulism symptoms develop relatively slowly, over several days compared to nerve agent effects, which can be instantaneous.

Interesting that atropine is mentioned as an enhancer of the toxic effects.
Edited by Mad_Larkin (05/06/11 04:37 PM)
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Salomon
ಠ︵ಠ balance ಠ_ಠ weaver ಠ‿ಠ

Registered: 01/17/09
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Re: Peptide psychedelics? [Re: Mad_Larkin]
#14411218 - 05/06/11 04:37 PM (12 years, 9 months ago) |
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shroomery: creating the next LSD one day at a time
-------------------- EVERYTHING EVENTUALLY BECOMES A DESERT
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Caine
lab rat



Registered: 01/25/10
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Re: Peptide psychedelics? [Re: 2Cents]
#14411223 - 05/06/11 04:38 PM (12 years, 9 months ago) |
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Quote:
2Cents said:
Quote:
SamuelLJackson said:
Quote:
2Cents said: ....what the fuck is a peptide psychedelic?
as of now, a hypothetical hallucinogenic protein.
So it's not something yet synthesized? Any links to this hypothetical protein research or is this a lone shroomerites crazed ramblings?
Crazed ramblings? It's not really that complicated  I'm just asking if anyone's heard of peptides that affect the 5-HT2A receptors.
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2Cents



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Re: Peptide psychedelics? [Re: Caine]
#14411232 - 05/06/11 04:41 PM (12 years, 9 months ago) |
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No offense mate, just curious.
-------------------- Long live the Shroomery!!!
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Mad_Larkin

Registered: 11/29/07
Posts: 18,606
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Re: Peptide psychedelics? [Re: 2Cents]
#14411241 - 05/06/11 04:42 PM (12 years, 9 months ago) |
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Crazed ramblings up in this motherfucker. 
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The Whale

Registered: 11/01/10
Posts: 2,384
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Re: Peptide psychedelics? [Re: Caine]
#14411293 - 05/06/11 04:52 PM (12 years, 9 months ago) |
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Quote:
Caine said:
Quote:
2Cents said:
Quote:
SamuelLJackson said:
Quote:
2Cents said: ....what the fuck is a peptide psychedelic?
as of now, a hypothetical hallucinogenic protein.
So it's not something yet synthesized? Any links to this hypothetical protein research or is this a lone shroomerites crazed ramblings?
Crazed ramblings? It's not really that complicated  I'm just asking if anyone's heard of peptides that affect the 5-HT2A receptors.
I could find the article if you'd like, but newer research suggests tryptamines involve more than just the 2A receptors (DMT was used in their lab). Additionally, some 2A agonists - including some medicines - don't even produce psychoactive effects. Peptides are pretty dense in the body and have widespread distribution as neurotrasmitters. Check out: Substance P. But they seem mostly to be involved in hormone behavior, so tinkering with these guys will likely grant control of the autonomic nervous system but not so much cerebral cognitive functions (I don't imagine). Although the behavior of ketamine, surprisingly, is subjectively "heady" despite focusing on NMDA. Meaning, we could target things like peptide-hormones and still end up tripping.
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Caine
lab rat



Registered: 01/25/10
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Re: Peptide psychedelics? [Re: The Whale]
#14411327 - 05/06/11 04:59 PM (12 years, 9 months ago) |
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Quote:
The Whale said: I could find the article if you'd like, but newer research suggests tryptamines involve more than just the 2A receptors (DMT was used in their lab). Additionally, some 2A agonists - including some medicines - don't even produce psychoactive effects. Peptides are pretty dense in the body and have widespread distribution as neurotrasmitters. Check out: Substance P. But they seem mostly to be involved in hormone behavior, so tinkering with these guys will likely grant control of the autonomic nervous system but not so much cerebral cognitive functions (I don't imagine). Although the behavior of ketamine, surprisingly, is subjectively "heady" despite focusing on NMDA. Meaning, we could target things like peptide-hormones and still end up tripping.
Yeah, that's what I'm wondering, just because we really know nothing about mechanisms of psychedelic drugs, but there certainly are peptides with activity at neural receptors, like endorphins.
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mellowparty
legitimate researcher


Registered: 05/17/09
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Re: Peptide psychedelics? [Re: Caine]
#14411331 - 05/06/11 04:59 PM (12 years, 9 months ago) |
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Sweet idea
Endorphines are extremely potent compared to opiates so I dont see (at least in theory) whats stopping the possible existence of a protein that would form very cohesive non-covalent interactions with the hydroxytryptamine receptor.
Hit folding@home for some help with the protein engineering. Once you get that I'll write the gene for you, clone it in an adenoviral/exosome vector carrying vehicle and inject you in the brain with a pressurized syringe.
Balls will be tripped. I guess you'll have to forget about your 5HT receptors afterwards as these will be heavily endocytosed but it will be the ultimate psychedelic journey
Is there a pdb entry for any 5TH receptor. That will be your starting point
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Beanhead
IS IRONIC PARADOX


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Re: Peptide psychedelics? [Re: The Whale]
#14411341 - 05/06/11 05:02 PM (12 years, 9 months ago) |
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Enkephalins sounds cool aswell
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Caine
lab rat



Registered: 01/25/10
Posts: 3,920
Loc: NE
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I'll check the PDB and update this post in a minute...
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Caine
lab rat



Registered: 01/25/10
Posts: 3,920
Loc: NE
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Re: Peptide psychedelics? [Re: Caine]
#14411414 - 05/06/11 05:18 PM (12 years, 9 months ago) |
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This is as close as I could get it seems, cool nonetheless
http://pubs.acs.org/doi/abs/10.1021/ci100402f
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mellowparty
legitimate researcher


Registered: 05/17/09
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Re: Peptide psychedelics? [Re: Caine]
#14411418 - 05/06/11 05:20 PM (12 years, 9 months ago) |
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I hate structural biology but I like this paper  
Good post man
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The Whale

Registered: 11/01/10
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From the abstract: "The results show that the model can be used in drug discovery for virtual screening and structure-based ligand design as well as in GPCR activation studies." Interesting.
You would have more success posting this at Bluelight. There are informed chemists afoot.
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Beanhead
IS IRONIC PARADOX


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Re: Peptide psychedelics? [Re: Beanhead]
#14411429 - 05/06/11 05:22 PM (12 years, 9 months ago) |
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