N, (4-Bromobenzyl)-Mexamine

[blueberries]

I was looking through the paper; Influence of Amine Substituents on 5-HT2A versus 5-HT2C Binding of Phenylalkyl- and Indolylalkyl- amines: Glennon et al., and found that among the probable starter compounds that Nichols used to find the NBOMe set of compounds, there was another of significant value.

That compound was N-Methyl-(4-Bromobenzyl)-Mexamine:

While the other Mexamine analogues tested did not show much, this compound showed highly potent and selective 5-HT2a agonism, some 10x the potency of 2C-B. However, as with the 2C-B counterparts, which all showed similar affinities with similar analogues, this one was unique amongst it's analogues, suggesting any enhancement on the phenyl ring would be worthless.

Has this been looked into more? Perhaps a 4-HO compound may be more useful with a slightly lower potency, while retaining this selectivity (I doubt it but it's a possibility).

EDIT: Sorry got the name wrong in the title, could someone change it? Thanks.

 

[Solipsis]

How selective is it outside of the few 5-HT receptors it was screened against, is what I'd want to know.

I find this particularly interesting because of the general idea that N-substitutions beyond allyl are basically not fruitful, then here is one that has a big fat mono-substitution on the amine.... soo maybe if you check mono substitutions, it gets interesting once you start compensating for it being a mono-substitution by using some bigger moieties?
And all the while thinking about electronegative aspects as well, so if not aromatic one might want to branch an alkyl with electronegative groups...?

 

[sekio]

It's selective for 5ht2a alright, it just lacks agonist activity, which means it's useless for a psychedelic. It's been tested in humans before.

Just another pitfall... affinity for a GPCR doesn't predict activity! Or lisuride would be a psychedelic.

 

[Hammilton]

That's not a bromobenzyl, that's bromophenyl

 

[blueberries]

It's selective for 5ht2a alright, it just lacks agonist activity

Do you have a source?

In the paper it suggests otherwise:

"Furthermore, whereas the binding data in Table 2 suggest that the iodo phenylalkylamine 18 may behave as an agonist and the bromo phenylalkylamine 17 as an antagonist, the situation is reversed in the indolylalkylamine series. That is, with a 52-fold difference, the bromo indolylalkylamine 33 is suggested to possess agonist character, whereas the iodo derivative 34, with only a 3-fold difference, may be an antagonist."

I realise it's only estimation however, so I'd love more info on it.

That's not a bromobenzyl, that's bromophenyl

I thought it was interchangeable as they use the expression bromobenzyl throughout the paper. Also in my Marvin program, it's labelled as a benzene ring, not a phenyl. I've always been a bit uncertain of the difference myself though.

 

[Solipsis]

How concerning is the slight resemblance to melatonin? I wouldn't want something messing with those hormonal systems, unless it was a melatonin analogue acting as an analogue found to be safe.

 

[Hammilton]

Benzyl would have a carbon between the amine and the benzene ring, phenyl is connected directly, you've just drawn it wrong I think

 

[blueberries]

Benzyl would have a carbon between the amine and the benzene ring, phenyl is connected directly, you've just drawn it wrong I think

Ah yeah, I see what you mean. Honestly I think I forgot that the carbon atom is an actual atom not just a bond. I get so engrossed with it all I forget the little things sometimes!

 

[DL-ark]

Mexamine itself has agonistic activity on 5-ht2a receptors and his highly selective for all 5-ht receptors (sans 5-ht3, which is great.)

Mexamine even has anecdotal evidence suggesting it has very psychedelic properties in doses of 100mg or possibly less.

 

[Limpet_Chicken]

I wonder what could come of mexamine+MAOI, something like a combination with harmala or yage.

Can you give any refs for that claim of psychedelic activity at high doses?

 

[DL-ark]

^

It seems to be active without a maoi when snorted. It sounds like it has some of the effects of lsa ( sudden euphoria, slight visuals)

http://www.erowid.org/experiences/exp.php?ID=16396