25i-NBOMe pharmacology

[Incunabula]

How much is known of the pharmacology 25i-NBOMe? I know that it is a highly potent agonist for the 5-HT2A receptor, mediating psychedelic effects.

I'm wondering if it is known to have any inhibiting or releasing effects on dopamine or serotonin?

I myself, believe that 2C-I has some inhibition or release of serotonin, as I get jaw clenching on it. And the day after can sometimes be just a little bit like the day after MDMA. But also just to a slight degree.
I haven't tried DOI, but it also sounds highly stimulating from what I've read.

 

[cannibalsnail]

2C-I is an alpha-x receptor agonist so produces body effects like a rise in Norepinephrine/Dopamine. 25I-nbome is too potent for these same issues to arise.

None of them affect the monoamine transporters.

 

[Incunabula]

an alpha-x receptor agonist

What' s that? You mean norepinephrine agonist receptor?

 

[cannibalsnail]

It may well bind to other receptors but Alpha-2 (nor/epinpehrine) receptor is its main effector.

 

[sekio]

As far as I know the -NBOME series primarily has affinity & activity at 5-HT2a and 5-HT2c receptors. They are more "selective" over the parent phenethylamines.

The actual 2c- series has significant affinity for the alpha/beta adrenergic receptors and even SERT, but I don't think the NBOME compounds share this.

Also, jaw clenching is a physical symptom and is not caused by any one receptor being activated. Don't be too quick to attribute that to "other" effects.

 

[ebola?]

The actual 2c- series has significant affinity for the alpha/beta adrenergic receptors and even SERT, but I don't think the NBOME compounds share this.

IIRC, those NBOME compounds tested for binding affinities DID show significant adrenal activity. When we say that they're highly selective, we mean for 5ht2a over other subtypes. I should look at the Nichols paper or the relevant dissertation (forgetting who that was) again though. Also, IIRC, only a couple 2c compounds have significant affinity at SERT or NET.

ebola

 

[Incunabula]

Also, jaw clenching is a physical symptom and is not caused by any one receptor being activated. Don't be too quick to attribute that to "other" effects.

What do you mean by "other" effects? As far as I know, bruxism is an indirect result of an imbalance between serotonin and dopamine, when talking about drug induced bruxism anyway. Could you please elaborate on your view of this.

.........only a couple 2c compounds have significant affinity at SERT or NET.

ebola

Which ones?

 

[sekio]

bruxism is an indirect result of an imbalance between serotonin and dopamine, when talking about drug induced bruxism anyway.

I think you're wrong here. High levels of 5-HT/DA are associated with bruxism but I don't think they are the direct causative agent... I bet it's something more like an adrenergic receptor.

 

[atrollappears]

I'm wondering if it is known to have any inhibiting or releasing effects on dopamine or serotonin?

I myself, believe that 2C-I has some inhibition or release of serotonin, as I get jaw clenching on it. And the day after can sometimes be just a little bit like the day after MDMA. But also just to a slight degree.
I haven't tried DOI, but it also sounds highly stimulating from what I've read.

The NBOMe part would certainly abolish any releasing ability, and nothing in that dose range would be active as a releasing agent anyway. IIRC 2C-I does not act as a reuptake inhibitor in the relevant concentration. My guess is that direct agonism is responsible for the effects of both 2C-I and the NBOMe.

It may well bind to other receptors but Alpha-2 (nor/epinpehrine) receptor is its main effector.

Alpha 2 agonism will decrease NE release and either raise or lower DA release depending on the circumstances. An example of an alpha 2 agonist is clonidine, an antihypertensive, ADHD, and off-label anxiety drug.

What do you mean by "other" effects? As far as I know, bruxism is an indirect result of an imbalance between serotonin and dopamine

"imbalance" is a very vague word. We know that MDMA and amphetamine, among other drugs, cause bruxism. The commonalities are norepinephrine and dopamine (or maybe not even dopamine because MDMA might not elevate dopamine from what I've seen). We know that bruxism is generally caused by myotonic muscle responses, which can in turn be caused by epinephrine. So, my guess is that epinephrine causes it with either drug, though perhaps it is not the only factor at play.

 

[Incunabula]

.... Also, IIRC, only a couple 2c compounds have significant affinity at SERT or NET.

ebola

Thanks a lot for the answers, people.

Were can I find more information about which 2c compounds that have affinity for SERT, NET or DAT?

 

[Coolwhip]

The commonalities are norepinephrine and dopamine (or maybe not even dopamine because MDMA might not elevate dopamine from what I've seen).

Sorry to go off topic, but I'm interested in what evidence you are basing this off of.

 

[atrollappears]

Sorry to go off topic, but I'm interested in what evidence you are basing this off of.

Oh jeez, I just looked up the study I got that from and realized I totally misread it. It was saying that MDMA's DA release wasn't really significant compared to mephedrone's or amphetamine's, and I took that to mean MDMA didn't cause significant DA release, "significant" in the statistical sense. So completely disregard that

 

[nirvus]

this is an interesting thread. my suggestion (take with salt): probably in vitro data is not available for nbome receptor affinities (PLEASE correct me if wrong (and a link would be awesome)). but an intelligent guess COULD be extrapolated from 2c-x binding data combined with an experienced psychonaut's intuition. I know, not scientific enough for publication, but. . . I don't know if in vitro data exists for 2c-x, but there has been some interesting in silico work done in this area. (http://pubs.acs.org/doi/abs/10.1021/ci100402f) <- this is the paper about the computer model they used to generate some theoretical binding data for a pretty large library of compounds including 2c-x and nbomes. the theoretical binding data is in the supplemental pdf file here: http://pubs.acs.org/doi/pdf/10.1021/ci100402f. scroll down a bit in that and there's a pretty awesome data set.

another thought: bruxism and subjective mental effects are pretty complex phenomenon. don't forget that in addition to direct effects at monoamine receptors, there are downstream effects between these and other signal pathways. put it this way: serotonin is pretty heavily involved in modulating other pathways' transmission. a strong effect at a neuromodulatory junction (like 5ht2a) probably alters transmission at other major neuromodulatory pathways, like DA and NE, GABA, Glutamate/NMDA, acetylcholine, etc. So, activity of endogenous neurotransmitters could be modified by activity of exogenous ligands (ie, drugs like nbome) at serotonin receptors in addition to (and independent of) the drugs actual effects from possibly binding to the other major regulatory receptors. just food for thought. remember what the doormouse said!

edit: my 69th post. lullzorz.8(