Phenethylamines Dextro Isomer Psychedelics

[PepperSocks]

So, after some decent experience with experiencing the vast difference between racemic amphetamine and the pure dextro isomer amphetamine it brought to mind the question; What if we were obtaining the pure dextro isomer of all these goodies we have?

I'm not sure how this relates to tryptamines but with phenethylamines I'm sure it relates.

Racemic amphetamine has a lot of peripheral side effects; that wired, jittery, bug eye effect of PNS stimulation. Dextro amphetamine is clean CNS stimulation with little side effects. It makes me wonder why Adderall is even a prescription drug; why the heck not just give people the more refined version with fewer side effects that's easier on the body and mind (lower heart rate, less anxiety, etc.). Part of me thinks that the side effects are what make it less desireable, thus people stop when they feel "wired" and are less likely to become addicted.

I got thinking about peripheral side effects of psychedelics and how having pure dextro isomers might feel (based on my effects of dextro amphetamine).

For example; dextro MDMA, dextro 2C-B, it would possibly be so clean and direct if the theory carries over.

 

[Solipsis]

I imagine it would not be cheap, but awesome stuff indeed!

On the other hand, maybe dextroamphetamine is very nice and clean feeling but the levo isomer plays its part on acting on the body.
Take 2C-B now for example, it could be that you lose some of the marvellous body high effect and tactile enhancement that connects the senses of your body to the psychedelic mental effects.
Dextro 2C-B might make for a terrific mental psychedelic but could feel like its missing something. It's at least a possibility. With MDMA I don't know, the dextro could be amazing on its own. But again, it's a complex drug and you might lose a part of what can make the magic.

Tryptamines are often great just the way they are if you ask me. Definitely the substituted ones.

 

[greenmeanies]

Phenethylamines do not have levo/dextro enantiomers. They do not have a chiral center. A couple special 2C-X do have chiral centers, but this is because the 4-position substituent is chiral (2C-T-17, 2C-G-5)

Amphetamines have a chiral center, because at the alpha carbon there are four distinct groups: hydrogen, amino, methyl, and benzyl.

also if i recall correctly, the active enantiomer of the psychedelic amphetamines (MDA, DOM, DOC) is the opposite of the active enantiomer of MDMA and the stimulant amphetamines.

The only two tryptamines that I can think of for chiral centers are AMT and 5-MeO-AMT. Again we have the alpha position substituted by four distinct groups (hydrogen, amino, methyl, and indolylmethyl). I'm not sure which enantiomer is responsible for the major effects of these drugs.

EDIT: quote from TIHKAL: alpha,O-DMS (5-MeO-AMT)

An additional complication and opportunity is provided by the fact that the placement of the methyl group on the alpha-position introduces a chiral carbon. The R- and S-isomers have been compared (see in the Qualitative Comments section) and the S-isomer is clearly three or four times more potent that the R-isomer. These were assayed completely blind, with the code having been broken only after the completion of the study. The dramatic differences in potency let the assignment of the more active isomer be made without hesitation. This S-isomer is the d- or dextrorotary one, and has the absolute configuration of the active member of the isomer pairs of amphetamine, of methamphetamine and of MDMA. All the psychedelic amphetamine derivatives (all that have been assayed, that is) have the R-isomer as the more potent one.

to summarize:

AMT, 5-MeO-AMT, AMP, MAMP, MDMA are all noticeably more active for the S/dextro enantiomer.
DOB, MDA, ALEPH, and all the 3C-phens are noticeably more active for the R/levo enantiomer.

 

[pharmakos]

the only chemical in pihkal that is more active with the (s) isomer is MDMA. the (r) isomer is more active for all of the other pihkal compounds with a chiral center. (edited out the bit i had wrong. sorry greenmeanies!)

as already stated, two-carbon phenethylamines (the 2C family) do not have a chiral center. three-carbon phenethylamines (amphetamines) do have a chiral center.

 

[TheAzo]

Wow, beaten by like 3 posts while i was typing this :-(

Dextroamphetamine is S-amphetamine using the more common R/S notation rather than the ambiguous D/L notation.

2C-X's do not have optical isomers, there are no asymmetric carbons. Neither do the tryptamines (except alpha-substituted ones, of course)

psychedelic amphetamines, as well as MD[M]A are optically active, and Shulgin investigated them in pihkal.

The S isomer (corresponding to dextroamphetamine) is not active as a psychedelic in the case of psychedelic amphetamines (DOx), with the R isomer carrying the majority of the psychedelic effects.
With MDMA, he found that the S isomer was the more active one, while the R isomer was much weaker, but still did something, and there is a suggestion that the racemate is better (then again, his entries for MDMA are not particularly typical in general). Opposite for MDA, where the R isomer is stronger, and the S isomer is weaker, but active; again, the conclusion was that the racemate was better than either pure enantiomer. What stood out to me reading the reports is that they were taking nearly the same doses of optically pure MD[M]A as they would have with the racemate, and getting similar or weaker subjective effects.

Pattern seems to be that for 5-HT2A agonists, the R isomer is better, for monoamine releasers, the S isomer is better. And that empathogens may be best as the racemate (though the sample is small, and shulgin et al often have odd taste in drugs) - this of course would tend to imply that the "magic" of stuff like MDA and MDMA is not just due to monoamine release, but due to a combination of monoamine release and direct 5HT agonism (which would explain why these new RC's with awesome looking release properties on paper end up falling short in vivo)

 

[PepperSocks]

Ah, yes, it's the alpha methyl that changes direction. Sorry about that. So yeah, no dextro 2C-B.

Interesting sentiments Solipsis; about the pure isomer possibly "missing something". I do think that when physically active racemic amphetamine to be more euphoric. There's more of a body buzz and moving feels more effortless. Dextro has less peripheral effects and that's good for low activity stuff but racemic can indeed be more fun while physical now that I think of it. I just seem to pay for it more with racemic; comedown/withdrawal is harder.

Also; I thought R = levo, S = dextro? greenmeanies would have it right that "S" stimulant amphetamines are the more active (dextro).

Interesting to note that DOx's have the levo isomer more active; but what about where it's active. Qualitatively would the the S isomer be more centrally active for instance?

 

[greenmeanies]

dextro/levo refers to how the pure compound rotates light. This optical rotation is based on various factors of the physical material, and is almost never correlated with the actual "absolute configuration" at the chiral center.

R/S on the other hand is the absolute configuration, based on the drawing of the structure.

Thus dextroamphetamine is the S-enantiomer, whilst other "dextro" compounds might be the R-enantiomer.

For comparing drugs in various classes where the dextro/levo is ambiguous, I would suggest we stick to R/S as that is determined by the structure drawing instead of optical properties.

In that case, it's probable that since S-AMP is the more active central stimulant and R-DOB is the more active central hallucinogen, perhaps S-DOB is the one that is responsible for the lingering stimulation after the psychedelic effects have worn off.

 

[TheAzo]

dextro/levo refers to how the pure compound rotates light. This optical rotation is based on various factors of the physical material, and is almost never correlated with the actual "absolute configuration" at the chiral center.

Nope - +/- notation refers to optical activity. Dextro and levo sometimes are used incorrectly in that manner, but, they're supposed to refer to the structural orientation using glyceraldehyde as a reference *rolleyes*
Really, a very backwards way of specifying chirality.

In that case, it's probable that since S-AMP is the more active central stimulant and R-DOB is the more active central hallucinogen, perhaps S-DOB is the one that is responsible for the lingering stimulation after the psychedelic effects have worn off.

I wouldn't be surprised - but i wouldn't be surprised if that wasn't the case either.

 

[LivingOnValium]

Racemic amphetamine has a lot of peripheral side effects; that wired, jittery, bug eye effect of PNS stimulation.

I disagree. This is something that's vastly exaggerated in BL. Sure there's a bit more peripheral side-effects with dl-amphetamine then there's with d-amphetamine. But d-amphetamine is far away from being free from the peripheral effects.

Personally i like the "more aggressive" nature of racemic amphetamine.

 

[greenmeanies]

Nope - +/- notation refers to optical activity. Dextro and levo sometimes are used incorrectly in that manner, but, they're supposed to refer to the structural orientation using glyceraldehyde as a reference *rolleyes*
Really, a very backwards way of specifying chirality.

thanks for the correction. It's really great that there are three ways of talking about chirality, and there are two different D/L vs d/l conventions.

According to wiki, dextro/levo can be shortened to lowercase d/l or (+/-) as they are all talking about optical rotation. This system is for experimental data: you put the compound into a polarimeter, and measure the rotation of light that passes through the sample.

R/S is absolute stereochemistry that refers to the specific ordering of the substituents around the chiral center. It has no correlation to the dextro/levo system.

The glyceraldehyde system uses small-caps "D" and "L" and also does not correspond to the dextro/levo system. For example, small-caps "D"-fructose is optically levorotary so you could call it (-)/l-fructose. however it is quite convenient for biochemists as most naturally-occurring amino acids are "L" (like L-tyrosine, L-tryptophan, etc) while most naturally occurring sugars are "D" (D-fructose, D-xylose, etc)

ouch, my brain

 

[nearjat]

You guys make me wanna take organic chemistry.

 

[Mjäll]

What an interesting topic. Some pieces fell onto the puzzle by reading this and related articles.



I second nearjat.

 

[cj187]

bump