DON and 5ht2a

[yaesutom]

So any idea how the nitro group affects the receptor, compared to a DO-halogen?

The stuff is easy to make .

 

[BilZ0r]

So so; this 3D-QSAR paper cites multiple references for (-)DONs 5-HT2A receptor affinity to be 210nM, vs 10nM for (-)DOI and 60nM for (-)DOM. So you've expect the dose needed would be somewhere around 10x DOI.

However, at the same dose as DOI, Shulgin 2nd references a a pretty unpleasant experince.

Sounds like I'd leave it out unless I was really keen for an "experience". But I reccomend the Shulgin approach, if it feels bad at a low dose, it probably is bad.

 

[fastandbulbous]

None at all - due to the charge separation going on with the nitro group it doesn't really fit the Nichols model of the 4-substituent being more potent with increasing lipophilic nature.

After re-reading the entry for DON from BilZ0r's post, I think I might have a bit of an idea about some of the nastyness:-

It's an aromatic nitro compound and lots of these are known to be toxic because of their ability to decouple respiration from oxidative phosphorylation (in the world wars, people who worked in munitions factories developed all sorts of nasty conditions because a lot of explosives (TNT, picric acid etc) are aromatic nitro compounds. Even in the lab, things like nitrobenzene & 2,4-dinitrophenylhydrazine have to be handled with care because of their toxicity.

The symptoms of decoupling oxidative phosphorylation are hyperthermia as all the energy of respiration is released as heat rather than going into making ATP.

The visual changes were intense. I felt I was running a slight fever, and was restless, but there was almost no physical malaise.

That's from the PIHKAL entry for DON - too close to the symptoms of said poisoning for me to want to try it.

PS - I think aromatic nitro compounds (or their reduced form, anilines/aromatic amines) are also linked with things like cancer and the immune system going funny. That's why all sorts of azo dyes were removed from foods

 

[whiterasta]

I am a former R/D chemist in the Diazo dye industry....I have organic brain syndrome due to said effects of various aromatic nitroso compounds and a very faulty fume hood.
Para-amino-morpholino-diethoxybenzene, and many other percursors and solvents damaged my brain enough to show on a cat scan and when I left there after three yrs I could barely speak coherently.I spent much time in the lab not conversing anyway so I did not really notice till I took a vacation away and began to clear my head. I was pretty sick for about a yr and have recovered much lost function,
however I have niether the will or desire to ever use this Ochem degree again ,save for my own amusement
As for the subject substance...some of the possible metabolites are pretty spooky.
Hope this helps a little.
WR

 

[C6H6]

I think you're jumping to conclusions here, F&B. It's true, many aromatic nitro compounds are toxic and/or mutagens. But many are not and are useful and commonly perscribed medications: clonazepam, nitrazepam, chloramphenicol are just a few examples. The nitro group in also not metabolized to the azo moiety of carcinogenic dyes.

The problem I can see with DON is that the NO2 gets reduced to NH2 in vivo, and this could well be an active metabolite since 4-NH2-amphetamines are known to be pharmacologically active. This metabolite could be the reason for the reported strong stimulation.

 

[Smyth]

There is a report of DON over in TR if anybody is interested.