Novel Putative Bicyclic Psychedelics?

[fastandbulbous]

^ 3,4-DMPEA fits into the active site of MAO without preventing it's conformational change to the active form, which means it gets chewed up and enough never reaches the bits of the brain it needs to reach to exert an effect. The reason mescaline is active is because the close grouping of the 3,4,5-trimethoxy groups means it doesn't fit the active site in a way that allows conformational change of MAO to the active form. The slight change of moving one methoxy group to give 2,4,5-TMPEA results in an inactive compound as the 3,4-substitution pattern seen with catecholamines isn't sterically hindered by the third methoxy group on the 2 position, hence it's chewed up & spat out by MAO.

Equally, 2C-T (2,5-dimethoxy-4-methylthioPEA) is active because replacing the 4-position oxygen of 2,4,5-TMPEA with a sulphur atom (directly below oxygen in the periodic table) results in a molecule that doesn't fit properly into the active site to allow the active form of the enzyme & hence isn't chewed up & deactivated by MAO (also probably accounts for the significant MAOI activity of the 2C-T-x/aleph series)

As to the fate of the 3-benzazepines, I defer to the great god, Fuckknows!

 

[LuxEtVeritas]

These 3-Benzazepines have huge potential as novel, non-analog psychedelics. .

Might be a bit of a stretch, but they do contain the PEA skeleton and are potentially consideed analoguers as closed conformation PEA analogues similar to the isoquinolones, et al and thus may under US law be looked upon as analogues

 

[Holy_cow]

The 3-benzazepines might also have to have some kind of alpha methyl substitution, because they are only restricted conformational analogd to PEA's, Just because they exhibit potent receptor binding numbers , doesn't mean they will exhibit the same properties in-vivo.

Some 3-benzazepine are enough efficiacous at 5-HT2C receptors and have other favorable pharmacological properties that it's evaluated as weight-loss drugs at 10mg. Changing the substitution pattern will make an equally efficiacous 5-HT2A agonist (psychedelic). It's all published, all data are there and only need thorough analysis. I think there are no open questions and no guesswork to do here, just a synthesis of the right compound. Only trouble: the synthesis of the 5-HT2A agonist 3-benzazepine isn't easy

But no doubt, we have new class of psychedelics, in addition to the PEAs and tryptamines. I wonder that Nichols hasn't picked up these structures yet.

 

[Ham-milton]

I don't think that these can be considered a distinct class of psychedelics. Like Lux said, they're essentially closed conformation PEA analogues.

 

[Holy_cow]

Might be a bit of a stretch, but they do contain the PEA skeleton and are potentially consideed analoguers as closed conformation PEA analogues similar to the isoquinolones, et al and thus may under US law be looked upon as analogues

It's a far stretch fom a PEA to a 3-benzazepine, but if it doesn't bear the common, well-known aromatic (2,5-dimethoxy-4-something) substituents of PEA hallucinogenics, you can't convince and court that it's an analog.

 

[Holy_cow]

I don't think that these can be considered a distinct class of psychedelics. Like Lux said, they're essentially closed conformation PEA analogues.

That's because you're not considering the aromatic substitution. Besides, all konwn PEA psychedelics loose their activity if the primary amine is further substituted. But 3-benzazepines are secondary amines. Show me one secondary amine that a proven psychedelic.

 

[LuxEtVeritas]

^ from a purely chemistry based standpoint i totally agree, but from the warped and corrupt legal universe we inhabit it is in the least gray enough to certainly not want to be in court defending oneself on said grounds

again though as stated prior in other threads (and though again note the term warped and corrupt still apply of course) proof of clear human use intent should need to fall on the burden of the prosecutor as analogues have the notable inclusion above directly scheduled entities to be of discernable human use intent

 

[Ham-milton]

And I agree as well, but just because technically it isn't doesn't mean the law is going to see it that way.

I can't see any prosecutor not seeing the connection between these any pea's.

 

[panic_the_digital]

Lorcaserin is now approved, should hit the market late this year, early next. Considering how fat this country is, getting a hold of some shouldn't be too difficult. As far as I know, this is the first pill that has been scheduled for the fact that it causes hallucinations

 

[Cortexiphan]

Show me one secondary amine that a proven psychedelic.

N-benzyls are pretty active, right?

In any case, I would like to see some 5-HT2B numbers on these compounds. They look like a heavy dose of cardiac valvulopathy to me.

 

[endotropic]

Lorcaserin is now approved, should hit the market late this year, early next. Considering how fat this country is, getting a hold of some shouldn't be too difficult. As far as I know, this is the first pill that has been scheduled for the fact that it causes hallucinations

It seems like the major concern was the euphoric properties, and hallucinations were more of a one off thing at 40mg at least (skip to slide 105 for the good stuff):

http://www.fda.gov/downloads/Adviso...MetabolicDrugsAdvisoryCommittee/UCM248406.pdf

 

[bolinas]

The abuse potential was literally at the bottom of their list. Above it you find "valvular heart disease", "depression/suicide", "cognitive impairments", "serotonin syndrome" and "carcinogenicity" and below it you see "PPH?", in other words, theoretical hypertension from the drug. Compared to the other effects, PPH and abuse potential are more minor problems.

 

[Black]

N-benzyls are pretty active, right?

In any case, I would like to see some 5-HT2B numbers on these compounds. They look like a heavy dose of cardiac valvulopathy to me.

according to wikipedia

Lorcaserin has shown 100x selectivity for 5-HT2C versus the closely related 5-HT2B receptor, and 17x selectivity over the 5-HT2A receptor

sadly i don't have access to the full text of their source.

 

[NeuroPsyence]

That's because you're not considering the aromatic substitution. Besides, all konwn PEA psychedelics loose their activity if the primary amine is further substituted. But 3-benzazepines are secondary amines. Show me one secondary amine that a proven psychedelic.

How about:

25x-NBOMe
25x-NBMD
25x-NBF

etc.

 

[NeuroPsyence]

I wonder how substitution of other halides for the chlorine atom would affect the binding profiles of the benzaprines discussed here? Any speculation?

 

[sekio]

Some of these benzazepines are dopamine D1/2 agonists in theory usable as stimulants. I don't know how much substitution they will tolerate.