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(R)-4-Bromo-3,6-dimethoxy-1-aminomethyl-benzocyclobutane (TCB-2)

Holy_cow

Holy_cow

Bluelighter
Joined
Nov 29, 2007
Messages
171
(R)-4-Bromo-3,6-dimethoxy-1-aminomethyl-benzocyclobutane (TCB-2) is one of Nichols latest products, reported in J. Med. Chem. 2006, 49, 5794-5803. Results of the drug discrimination assay indicate that TCB-2 is equipotent to LSD and is theretofore the most potent phenethylamine hallucinogen ever reported. However, TCB-2 is different than other hallucinogenic 5-HT2A agonists due to the fact that it is a functionally selective agonist at the 5-HT2A receptor, having about 65-fold selectivity for the activation of the PLC signaling pathway over arachidonic acid release or 2-arachidonylglycerol (2-AG) production. Therefore, Nichols et al. argue that it might not be hallucinogenic in humans.

This compound is commercially available from one of the well known biochemicals suppliers (TCB-2, 10mg 150€), and I know that at least one person (a Bluelighter) has purchased and tasted it, but can't remember what he reported on the effects.

So, if you have sampled this compound, please share your experiences and post them here!
 
If someone could post the article by Nichols et al.

Because I don't have acces to the article and want to give it a read, it would be much appricated..
 
At the least human bioassays should make it so we can discern between the effects of PLC activation versus AA release/2-AG production (which will provide clues to making more interesting and specific psychedelic compounds).
 
^^ This would be fantastic. While I would have a lot of reservations about being the first human to try such a compound, this is perhaps the only way to shed some light on the question of which (if not both) post 5-HT2a receptor second-messenger signaling cascade contributes more to psychedelia. In vitro cell culture assays and animal drug discrimination studies just can't resolve these uniquely human issues of "pharmacotheology" and perceptual phenomenology. In other words, you simply cannot ask a mouse "how was your trip?" Well, you can, but if you get an answer, then chances are you were the one who was tripping.

I don't know if I like the structure of this one, though. Cyclobutyl moieties always make me a little uncomfortable...all that ring strain. What kind of metabolites might we anticipate?
 
Im not much of a psychopharmaceutist, more Plant metabolism oriented background so please forgive me, but, Nicols et al are saying is that due to the fact that this thing plays into 2-AG production the increased levels of Arachidonic Acid and that it is selective at the 5ht2a it is most likely not hallucinogenic. 2-AG is a endocannibinoid, what role Arachidonic Acid and 2-AG have in the 5ht realm?

Also, the one position on the BenzoCyclobutane RIng system is on the corner of the Butane, How is this a Phenethylamine?
 
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Beenhead said:
Im not much of a psychopharmaceutist, more Plant metabolism oriented background so please forgive me, but, Nicols et al are saying is that due to the fact that this thing plays into 2-AG production the increased levels of Arachidonic Acid and that it is selective at the 5ht2a it is most likely not hallucinogenic. 2-AG is a endocannibinoid, what role Arachidonic Acid and 2-AG have in the 5ht realm?
Click to expand...

the arachidonic acid is part of the secondary signalling system that allows the agonist activated receptor to interact with the rest of the neuron.

with 5ht2a agonists, there are at least two ways that activating the 5ht2a receptor can alter the neurons activity through altering metabolism in the neuron and releasing secondary messengers inside the 5ht2a receptor containing neuron, so this is not really related to 2AG or anandamide or arachidonic acid brain levels on a bigger scale.

1, the supposedly important one for traditional hallucinogenic action is PLA2 mediated and releases Arachiconic acid as a secondary messenger,
2 PLC related Inositol phosphate accumalation, this is not neccesarily associated with hallucinogenic activity, but most hallucinogens do also interact with this mechanism.

this discovery of differential secondary messengers makes a lot of the data on halucinogen activity meaningless, because typically hallucinogen activity was measured by looking at 5ht2a mediated Inositol Phosphate turnover, which of course threw up the lisuride problem, lisuride is a much more potent and effective agonist measured by IP turnover than LSD but it is almost without hallucinogenic activity.

Once again this is another example of how we are finding now that the whole field of G-protein coupled receptors is far more complex than was initially thought.

If you read between the lines in nichol's paper you will find the answer to whether TCB-2 is a traditionally active Hallucinogen in humans. ;)
 
Those that know if it is active or not are unlikely to want to confirm it, lest it become yet another "RC" subject to legislative attention.
 
Riemann Zeta said:
^^

I don't know if I like the structure of this one, though. Cyclobutyl moieties always make me a little uncomfortable...all that ring strain. What kind of metabolites might we anticipate?
Click to expand...

Speaking of synchronicities,I had the very same thought at the very same time yesterday,when travelling home in the train and watching the sun.Cyclobutyl on the Benzene,and an amine,hmmm...
 
low dosages are most interesting (less than 1mg orally) the material is lacking at higher dosages and seems never to give anything like the full psychedelic spectrum even at 5mg plus.
 
^^^

Very interesting, it is selective for just one of the intracellular trafficking pathways following 5HT2A receptor binding as I recall. So probably both pathways are needed for full psychedelic effects. Though very selective 5HT2A agonists do seem a bit lacking so far as full psychedelic effects go, it seems like 5HT2C, and probably 5HT2B and 5HT1A also have an important role.
 
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