BEAUTY'S MAGIC TRICKS

CONFORMATIONALLY CONSTRAINED TRYPTAMINE ANALOGS

What would happen if LSD and DMT explored "the erotic" and give birth to a child?

Conformationally constrained tryptamine analogs. Can we talk? Why was the last paper on this topic published in 1967? Why are we not all basking in the glory of 1,3,4,5-tetrahydrobenzoindoles? The above structure is a hybrid btw LSD and DMT, its affinity for the 5HT2a receptor is significantly less than that of LSD but a bit more than DMT, it may have oral activity, and it should be planar as heck! Well you know the world of speculative pharmacology is highly unsatisfying (total pharmacoblueballs) and all things must be tested in the human animal but wow - throw on an N,N-diethyl substituent, or a N-methyl,N-isopropyl sub and you're in business - you dig?

catch you on the flip side.

GEOMETRY AND BORGES

in the borges story death and the compass the final murder, which was supposed to occur on the forth point of a rhombus, is actually executed on the third point of an equilateral triangle. oddly, there is no way a fourth point added to an equilateral triangle can yield a rhombus* an equilateral triangle can compose half of a four sided polygon or at best a trapazoid, but a rhombus is composed of two isosceles triangles joined at the base, so thats my first confusion. my second confusion is in regards to the final shape the detective wishes to be executed upon in his next incarnation. the shape is drawn out above, a line segment starting at A with death occurring at D. what is the significance of this shape, is it referenced in kabbalistic literature? is it nonsensical (doubtful)?

*im defining rhombus as a four sided parallelogram without 90 degree angles, im aware certain definitions allow a

square to be a rhombus but that seems redic

PHARMACOGNATES?

i would like to stop for a moment to propose a new word:

pharmacognate ˌfärməˈkägˌnāt

adjective

1 Pharmacology (of a molecule) having a structural resemblance to its biological target on a macroscopic level: Prostaglandin E1 looks like an erect penis.

the crucial point in the above example is that Prostaglandin E1 looks like an erect penis* AND is used to treat erectile dysfunction. etymologically, pharma is from the latin pharmaceuticus "of drugs" & cognateis from cognatus "of common descent." i could probably think of a better word to suit this definition. not that it really matters because pharmacognate is almost never needed and is ultimately a useless example of pareidolia** furthermore when you consider many molecules are structurally flexible with rotating bonds it becomes an even more useless term (not that a molecular diagram is in any way an accurate representation of the "actual" molecule in the first place).

nonetheless, certain molecular diagrams do resemble various things, related or unrelated to their behavior. heroin looks like a horseshoe crab, imipramine looks like a kite, MDAI looks like something btw a larva and a bow-tie. they may be shapes in the clouds, man, but that does not mean their shouldn't be a poorly chosen word to describe (a minority of) them!

*with a hydroxylated urethra

** or is it?

SPEED 2: CRUISE CONTROL

Fun with trace amines and enzyme inhibition

I went to whole foods today and asked if they sold phenethylamine or PEA, they led me to their phenylalanine.

"No not phenylalanine - Phen-Ethyl-Amine"

"What's it do?"

"It's a stimulant"

"Oh no stimulant is not a Whole Foods word, cummon man, stimulant is not a Whole Foods word!"

PEA is a trace amine, putative neurotransmitter, and the chemical backbone of most dopaminergic stimulants. Additionally it's reported to be more addictive than amphetamine (of which PEA is the parent compound). It's unclear to me if this is because it's a qualitatively superior stimulant (likely) or because the shortened duration makes it fit the classic criteria for an addictive drug ((fast onset/short duration/frequent administration required) also likely) the reason that PEA has not gained widespread popularity is that it's almost immediately deaminated by MAO rendering it inactive moments after ingestion. There are two popular ways of overcoming the enzymatic tyranny of MAO, the first being direct inhibition via a pharmaceutical MAOI (with the MAO-B selective selegiline being most popular) and the second is to overwhelm MAO by taking megadoses in excess of a gram. With MAO-B inhibition the dose of PEA is comparable to amphetamine i.e., 25mg is reported to be very strong.

It seems to be a small minority of people that can play with the selegiline+PEA combo without getting miserably addicted, perhaps even a minuscule minority. In many ways it's the holy grail of stimulants: (arguably) safe, dirt cheep, and completely legal. Yet it's not something people can use responsibly. So how can one change this, how can one take advantage of this beautiful molecule which holds so much potential? PEA has a half life of 1 minute ((comp. to smoked crack which has a half life of 56 min) although PEA's t_1/2 must be longer with MAO inhibition (more research is required)) thusly it necessitates continuous redosing - the first solution is to create some kind of mechanical time release mechanism, I'll leave that to others. the second is to introduce a time release mechanism into the molecule itself á la vyvanse.

So here is my solution: lys-PEA aka alpha-desmethyl-lisdexamfetamine. a time release PEA prodrug, when taken with a MAOI it should have a long and healthy duration (I'm guessing something closer to normal dexamp sans lysine) a low dose, low toxicity, and ultra-low illegality. It will overcome the SAS criterion I outlined above and will probably be an incredibly effective ADHD treatment. The TRUE holy grail of psychostimulants. perhaps it would even be embraced by whole foods, after all lysine and phenethylamine are both TOTALLY natural. I only want to help people.

Equilibrium dissociation constants:

Phenethylamine: NE: 10.9; DA: 39.5; SE > 10000.*
Amphetamine: NE: 7.07; DA: 24.8; SE: 1765.
Methamphetamine: NE: 12.3; DA: 24.5; SE: 736.

*gotta love the way it gives 5HT the cold shoulder, harsh bro!

SPEED

I cant help but wonder about the nature of these two unnamed unstudied unsynthesized and generally unknown (tentative) psychostimulants - and by "wonder about the nature" i mean to say "obsess over the possibility" that they will be the most earth shatteringly powerful stimulants known to man which will usher in a new and sleepless era of hyperproductivity and total self-realization.

the molecule on the left is an analog of desoxypipradrol featuring the notorious 3,4-dicholoro substitution which sextuples the potency of methylphenidate, when added to the already perfect desoxypipradrol it could produce a stimulant fully active in the tens of micrograms.

the molecule on the right is the alpha-propyl homolog of buphedrone, elongating the alpha substituent in cathinones causes an increase in potency (the opposite effect is seen amphetamines) so one could imagine this chemical having a dosage in the general league of MDPV (whose subjective effects are toxic and miserable) but with no concern over a pro-oxidant dihydroxy conjugation ready metabolite (is that a legit concern ive never been sure?) i think its name should be penthedrone which has a nice ring to it - and im done.

UPDATE

OK, this blog does not really exist. This time last year I felt as if I should blog but my blog spirit is weak. I may try to change that though.

I'm speaking in a lineup with Laurie Anderson and David Wilson on Halloween at the Cantor Film Center, I will be talking about TTX, DiPT and other pharmacological oddities.

On November 4th I'm talking in a lineup with Alex Grey and Daniel Pinchbeck at Webster Hall: the topic will be ayahuasca.

Three new VBS episodes are being edited, and the new best of Vice book is out and filled with incredible articles including a revised and corrected version of The Magic Jews as well as A Giant Chinese Fingertrap Made Of rainbows Tried to Suck Me Into The Sky

Love,

hamitlon