Very regular use of DOx, TNF-a implications

[Limpet_Chicken]

This isn't because it affects me personally, I intend to direct someone to the thread if it takes off and produces any useful input.

But there is a subject (female if it makes a difference) thats been taking at one point, daily, some pretty staggering doses of DOx. DON in particular but afaik, others also. Possibly DOCN (does 2C-CN and the other 2Cx series share the same action?). So much so that I'm staggered tachyphylaxis doesn't set in. Or that they continue to have any effect at all.

I know DOI in particular has some fairly potent inhibitory effects on TNF-alpha release. And given the doses and regularity, daily, in largish quantities (6mg DON plus) whats the likeliehood of a rebound resulting in systemic proinflammatory effects, or generalized cytotoxicity? particularly concerned about damage to the heart. Subject describes burning of the skin (although had also recently been in hospital after a nasty incident, that afaik, involved a Br2 spill. So not sure if this was systemic or limited to the area contacted by bromine, although I think, the former)

 

[serotonin2A]

DOI is the only 5-HT2A agonist that has been reported to have a potent effect on TNFalpha. Other compounds were tested but did not produce the same effect.

 

[Limpet_Chicken]

Including the other halide DOx series? and the likes of DON or DOTFM? particularly thinking highly electronegative substituents at the 4' carbon of the phenyl. DON is a fairly unusual one isn't it as far as frequency of it turning up anywhere goes, frequency of use etc? Although this particular subject seems really to like the stuff.

Or does it include halides/pseudohalides with even DOB not sharing in the properties of TNF-alpha inhibition. Interesting if it is unique amongst the halide substituents as well, if so, is it known why?

 

[serotonin2A]

Including the other halide DOx series? and the likes of DON or DOTFM? particularly thinking highly electronegative substituents at the 4' carbon of the phenyl. DON is a fairly unusual one isn't it as far as frequency of it turning up anywhere goes, frequency of use etc? Although this particular subject seems really to like the stuff.

Or does it include halides/pseudohalides with even DOB not sharing in the properties of TNF-alpha inhibition. Interesting if it is unique amongst the halide substituents as well, if so, is it known why?

I know they tested a few other drugs, but I don't know the specifics. I doubt that they looked at DON or DOTFM.

Keep in mind that DOI was much more potent then would be anticipated based on its affinity. It is not yet clear if the effect is peculiar to DOI or is induced by other 5-HT2A receptor agonists.