O-4310: An interesting tryptamine

[Xerolad]

O-4310 seems to be a powerful 5ht1a-selective agonist with no 5ht1b activity. There seems to be almost no information out there about this one. Any Bluelighters know anything about this beyond the Wikipedia article?

 

[nuke]

The most potent likely psychedelic compound from that patent (thanks Organix! patent US7655691) is O-4244 or 3-(2-Dimethylaminoethyl)-6-fluoro-1-methyl-1H-indol-4-ol. It displays strong h5HT2A (0.55 nM for 61% IP3 turnover activity) and h5HT2C (0.66 nM for 75% IP3 turnover activity) partial agonist activity while having no activity at 5HT2B. This is on par with the other ultrapotents such as the NBOMe's and LSD, although at such high intrinsic activities I would have some worry about toxicity if one isn't particularly exacting about their doses.

 

[sekio]

O-4244 = 6-fluoro-1-methyl-psilocin
O-4310 = 6-fluoro-1-isopropyl-psilocin

Would this make 1-methylpsilocin active too? Or other 1-alkyl tryptamines?

Isn't 6-F-DMT non-hallucinogenic?

Maybe 1-acetylpsilocin? Along the lines of LSD --> ALD?

 

[infantannihilator]

the list of items to add to my stash just keeps growing and growing

I need to make this a job, not a hobby, if I ever hope to catch up and feel out each substance.

 

[Si Dread]

Ahhhh do this for a living..? Hahahaha nice dream!

It'd be good if my finances were expanding at the same rate as RC options Lol

 

[.:Holy::Toast:.]

I feel the same, the world of psychedelics is growing so rapidly, I wish I could say the same about my bank account.
Damn you post secondary education

 

[Solipsis]

I take it the talk of 5-HT1 receptors in the OP is a typo?

Furthermore, this is too theoretical for PD, I'm moving it over to ADD.

Call us when confirmed samples are in people's posession and bioassays are afoot.

Also, I don't know about you guys but even when wiki is one click away I feel that having structural formula's and data shown in the thread makes for integrated and comprehensive reading.

O-4310 (1-isopropyl-6-fluoro-psilocin) is a tryptamine derivative developed by Organix which acts as a serotonin receptor agonist. It is claimed to have an EC50 of 5nM at 5-HT2A with 89% efficacy vs 5-HT, and 100x selectivity over 5-HT2C, while being apparently inactive at the 5-HT2B antitarget.[1]

NSFW:

SUMMARY OF THE INVENTION
The present invention relates to novel N-substituted psilocin (4-hydroxyindole) derivatives that are also substituted at the 5-, 6-, and/or 7-positions and possess 5-HT2C receptor selectivity, preferably versus both the 5HT2A and 5-HT2B receptors. Such compounds have not previously been described or recognized to have selective functional activity at the 5-HT2C-receptor or to have in vivo activity in an animal model of human disease.

The invention also relates to N-substituted psilocybin (4-phosphoryloxyindole) derivatives, also substituted at the 5-, 6-, and/or 7-positions. Without wishing to be bound by theory, it is believed that such compounds act as prodrugs for the corresponding 4-hydroxy compounds in vivo (Jacob III, P.; Shulgin, A. T. in NIDA Research Monograph 146 (Hallucinogens, an Update), 2000, Eds. Lin, G. C.; Glennon, R. A., pp 74).

In one aspect, the invention provides a compound represented by the structural formula:

Figure US07655691-20100202-C00001

EC50 (nM)

0-4310 5 +/− 2 (89% ) Inactive 592 +/− 30 (~50% )

 

[mad_scientist]

The most potent likely psychedelic compound from that patent (thanks Organix! patent US7655691) is O-4244 or 3-(2-Dimethylaminoethyl)-6-fluoro-1-methyl-1H-indol-4-ol. It displays strong h5HT2A (0.55 nM for 61% IP3 turnover activity) and h5HT2C (0.66 nM for 75% IP3 turnover activity) partial agonist activity while having no activity at 5HT2B.

Indeed O-4244 may be the best candidate psychedelic, though O-4310 is the most 5HT2A selective. The 1-ethyl derivative O-4284 and corresponding 7-fluoro isomer O-3943 also look promising.

The fact it is active with a 1-alkyl substitution is one of the most interesting things about this compound imo. This does suggest other 1-methyl/ethyl/isopropyl tryptamines might also be active. Both 1-methylpsilocin and 6-fluoropsilocin are known compounds, albeit somewhat reduced in activity over psilocin in vitro, but I've never heard of them being bioassayed in humans. There was an old report I read once about 1-methyl-5-MeO-DiPT being active though, so that indole NH may not be required for activity after all. The 6-substitution may be a bit of a red herring, it is probably there mainly to reduce the 5HT2B affinity I'd guess, but most likely loses some affinity for 2A and 2C as well at the same time.

 

[atara]

The most potent likely psychedelic compound from that patent (thanks Organix! patent US7655691) is O-4244 or 3-(2-Dimethylaminoethyl)-6-fluoro-1-methyl-1H-indol-4-ol. It displays strong h5HT2A (0.55 nM for 61% IP3 turnover activity) and h5HT2C (0.66 nM for 75% IP3 turnover activity) partial agonist activity while having no activity at 5HT2B. This is on par with the other ultrapotents such as the NBOMe's and LSD, although at such high intrinsic activities I would have some worry about toxicity if one isn't particularly exacting about their doses.

Keep in mind also that binding numbers are not always perfect and that the NBOMe's had low 5-ht2b affinity as well, until they didn't.

 

[yaesutom]

Very exciting! I've always wondered what other possible "DMT like" molecules there can be (or psilocin like) out there undiscovered. I wonder if they would keep that "DMT feel" / natural, earthy feel that DMT/psilocin/4-aco-dmt have...