DR. LEHRER: I wonder if you could comment on the question of
transport of these substances into the brain. It's known that indoles and
catechols are more easily transported into the brain as the corresponding
amino acids; and I wonder whether some of the mescaline series of drugs
might not get into the brain more easily as the amino acids, and then become
decarboxylated?
DR. SHULGIN: The only one I know that's been studied that way is
the actual analog of mescaline itself, trimethoxyphenylalanine. It was synthe
sized in England and reported in the J.C.S., where it was stated that
"Pharmacology will follow." And about two years later, not having found it
I wrote, and was told, oh, yes, there was absolutely nothing of interest. Other
than that, I know of no amino acid studies in this area that would challenge
that. It would be a fairly simple series to make, I would think.
DR. BIEL: I don't know if they get decarboxylated.
The question I had was in regard to bufotenine. You ascribed rather low
activity to it
DR. SHULGIN: As far as being a psychotomimetic. There is no ques
tion but that it's biologically active, however.
DR. BIEL: Himwich recently published the correlation between the
appearance of bufotenine in the urine of schizophrenics and a gradual im
provement as urinary bufotenine levels went down or disappeared alto
gether. Does this alter the picture at all?
DR. SHULGIN: No. There's no question that bufotenine is a metabo
lite. It's been found not as an artifact but as a genuine component of urine.
I would mention that in the human trial with it (I think it was given
intravenously), a whole series of symptoms was observed, but I would
hardly call any of them psychotomimetic in nature. That's my only reason
for downgrading it. It's not the potency but the nature of the action. It's a
highly potent compound.
DR. DOMINO: People turn blue. There are marked cardiovascular
effects.
DR. GESSNER: We do have some preliminary data which make us
believe that the reason bufotenine is not found to be active is because it
simply does not get into the brain. If you put an O-acetyl group on it, it gets
into the brain, and then it's hydrolyzed back to bufotenine. It's quite active.
DR. SHULGIN: You haven't done it in humans yet?
DR. GESSNER: No.

No, it would be another compound altogether... To my knowledge 4-aco-dmt is not metabolized into bufo by the human body.

And HO is more potent by weight than ACO subsituted tryptamines.

Acolon 5's point about OH being more potent than AcO only applies to 4-OH because it can form an intramolecular hydrogen bond with the sidechain nitrogen. Just to reiterate

The idea is that this H-bonded cyclisation protects the sidechain nitrogen from MAO (and possibly other enzyme) attack, making it more potent in the sense that less gets destroyed by first-pass metabolism.

It is also possible that this cyclisation enhances crossing of the blood-brain barrier./quote]
But since we really know nothing on this topic, this reasoning can swing in either way with equal probability! Cyclisation could make a molecule more susceptible to first pass metabolism and decrease BBB passage.

[quote=downwardsfromzero]While I cannot offer any empirical evidence to support this, I would love to be in a position where I could investigate these propositions!

Cyclisation could make a molecule more susceptible to first pass metabolism and decrease BBB passage.

I don't know if you mean 4-aco-dmt which is an analog of mushrooms the acetylated version, and supposedly (THEORIZED) as psylocybin metabolized into psilocin, as does 4-aco supposedly this is a rumor though, my understanding is that 4-po-dmt is Psilocybin and(4-ho-dmt)is psilocin, 5-ho is bufo, I have not read anything stating that 4 aco metabolized into bufo but as said possibly into 4-ho, but I know nothing of 5-aco-dmt. Hope this helps

Yes he is talking about 5-AcO-DMT. O-Acetyl (AcO) bonds can convert to hydroxy (OH) bonds in vivo, so if one were to ingest 4-AcO-DMT/5-AcO-DMT/6-AcO-DMT/7-AcO-DMT, then the corresponding 4-OH-DMT/5-OH-DMT/6-OH-DMT/7-OH-DMT would theoretically be produced inside the body.