What's the most potent 25-I molecule ?

[MedicinalUser247]

What's the most potent 25-I molecule. I'm trying to do research on the 5HT-2a receptors. Do you know which one it is ?

 

[Dougie Doozer]

No clue but I'd guess 25B. I don't think 25E or DOET are as potent as you'd imagine, but my memory is fuzzy about that.

 

[Skorpio]

Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs) - PubMed

The binding profile of NBOMe drugs predicts strong hallucinogenic effects, similar to LSD, but possibly more stimulant properties because of α1 receptor interactions.

pubmed.ncbi.nlm.nih.gov

This paper looks at the binding affinities (and activation concentations) of various 2CX compounds and the NBOMe varients.

They find 25B-NBOMe is the most potent (binding affinity of 0.0005 uM) followed by 25I-NBOMe, 25E-NBOMe, and 25T4-NBOMe (all with a binding affinity of 0.0006 uM).

 

[MedicinalUser247]

Thanks. You see what I'm trying to do is design a 5HT-2a super agonist, but I'm only going by what already exists.

 

[Skorpio]

Thanks. You see what I'm trying to do is design a 5HT-2a super agonist, but I'm only going by what already exists.

Why? The 25X compounds are some of the worst and most dangerous psychadelics. Other super potent agonists like bromo dragonfly are just as problematic.

As a counterexample mescaline is a truly weak compound, and it is lovely.

 

[MedicinalUser247]

What releases more serotonin a furan or a methylenedioxy ?

 

[Deleted member 576750]

More isn't always better

 

[blazR]

OP, please investigate SAR

 

[MedicinalUser247]

Great point. What there needs to be is a reduction of the stimulating part of the structure. How to go about that I'm still not sure.

 

[Deleted member 576750]

What causes stimulation?

 

[MedicinalUser247]

Basically the propan-2-amine. Thats why I going to replace everything I design with a propane-1,2-diol to make it safer.

 

[Deleted member 576750]

But why does that cause stimulation? Like what is happening in the nervous system and to muscles and other organs such as the heart and why do those things happen?

 

[MedicinalUser247]

It's just how it works, but I honestly don't know.

 

[Deleted member 576750]

You seem awful sure that particular part of the structure is doing what you think it is, but you don't understand how?

How do the chemical properties of that structure impact the volume of distribution, what tissues does it end up in at the highest concentrations?

Which part of that structure is responsible for DAT and NET binding? How can you figure that out?

 

[Dougie Doozer]

Doesn't norepinephrine cause dopaminergic stim effects?

 

[Deleted member 576750]

Are you saying that norepinephrine release causes dopamine release? These are two different neurotransmitters with different functions and different circuits remember

 

[Deleted member 576750]

Also, what is dopaminergic stimulation?

 

[Deleted member 576750]

 

[Dougie Doozer]

Thanks that's the best summarizing slideshow ever! Is norepinephrine release or reuptake inhibition what makes mdma, coke and meth speedy?

 

[Deleted member 576750]

Both dopamine and norepinephrine can be stimulating. NE generally is associated with activation of the sympathetic nervous system which causes things like the increase in heart rate and blood pressure but dopamine can cause changes in the striatum to cause a person to physically move more. Too much NE release has also bee associated with muscle tremors. Its pretty complicated and there are multiple systems that you need to look at depending on what type of "stimulation" you're interested in