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Stimulants of the Future

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No, alkoxy groups - I understand that 3-methoxy-4-propionoxyamphetamine is active, (under 500mg but I cannot remember the actual dose). The 4-alkyl substituted ones are most probably active up to the 3/4 carbon chain, but I wouldn't say for definite as it's just theoretical musings about them

4-hydroxy compounds are not going to be active as there needs to be a hydrophobic group there for activity at 5HT2a and phenolic OH groups are fairly polar (and less likely to cross the BBB)
 
Au contraire mon frere,
DOAM is active.
des(2-methoxy)-DOAM will be active as well, no?

Also, having one hydroxyl group does not preclude necessarily CNS penetration; see psilocin, for example.
 
Church said:
All I know is that if some of you chemists would get to making a euphoric, entactogenic amphetamine, one that doesn't necessarily cause the user to have epiphanies and psychospiritual revelations, I would pay top dollar for it.

Or, if there are still some chemists out there who aren't pussies about making drugs that are specifically controlled or illegal, would you please flood the markets with more MDA and less MDMA? Thank you.

MDA = the best recreational drug EVER!!!
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I imagine that the route that these chemists are using is one in which involves tacking on one extra step for making MDA from it's ketone precursor. Other synthetic routes are longer to get MDMA, but the method most commonly used must be the former.
 
Not really, either MDA or MDMA can be made in one step from MDP2P/PMK using sodium cyanoborohydride in methanol and the appropriate amine or methylamine salt.

You can also get MDA from MDP2P/PMK using the Leuckart reaction which involves forming an amide following by hydrolysis. This method is messier but sound.
 
Helios. said:
Au contraire mon frere,
DOAM is active.
des(2-methoxy)-DOAM will be active as well, no?

Also, having one hydroxyl group does not preclude necessarily CNS penetration; see psilocin, for example.
Click to expand...

From PIHKAL:

QUALITATIVE COMMENTS: (with 10 mg) There was a clear threshold that in no way interfered with my day's activities. I was quite gay and voluble at lunch and bubbled on into the afternoon with puns and high spirits. There may have been a little motor incoordination as noted in handwriting, and there was a strange tenseness during driving. There were no sequelae, there was no trouble sleeping, and with this potency way down from the lower homologues, I have no pressing desire to take this compound to a higher dose.
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Don't sound active in any meaningful psychedelic way - in fact Shulgin's description of what happened sounds like it has more in common with alcohol than any psychedelic I can think of. Psilocin forms an internal hydrogen bond compound (forget the name of such things at the moment - my brain seems stuck on zwitterion, which it isn't) that somewhat negates the polar nature of the OH group; because of steric considerations, 4-hydroxyphenethylamines are unable to form such an internally hydrogen bonded compound
 
Helios:

Not really, either MDA or MDMA can be made in one step from MDP2P/PMK using sodium cyanoborohydride in methanol and the appropriate amine or methylamine salt.


You can also get MDA from MDP2P/PMK using the Leuckart reaction which involves forming an amide following by hydrolysis. This method is messier but sound.
---

Ok ok
You're right. But that was just a trap to see who knows too much for their own good. It was already obvious that you do ;)
I guess what I was thinking of was the synthetic route that most small time chemists would be using with precursor acquisition being a concern. I imagine sodium borohydride and cyano borohydride are harder to come by without raising eyebrows. But if you have the ketone in hand, hydroxylamine, aluminum foil and some mercury metal are easy to come by, but add an extra step since you have to form the oxime. If you consider that a step.
So why isn't there more MDA being produced? I imagine some of the big labs may even go through MDA as an intermediate before N-methylation to MDMA. Doesn't make good business sense. I suppose it's supply and demand. MDA freebase is even easier to distill than MDMA freebase isn't it? My knowledge is based on browsing the hive years ago, so don't use me as a reference. And it's highly unlikely that this big evil labs bother distilling the freebase anyways.

Fishing through my benzo destroyed memory, I also remember reading about the substituting PPA (or its isomers) with (pseudo)ephedrine via standard reaction conditions (whatever they were at the time, cyanogen bromide or the obviously less deadly method) . Apparently this wasn't a good drug candidate due to some adverse side effects. Does anybody know why?

And does anyone want to suggest what the effect of replacing the oxazoline ring with an oxazole ring. Extra double bond between the two quaternary carbons. I know this change in planarity is not insignificant, the only reason I bring it up is because the different diastereomers of the parent compound all show activity. So maybe the binding site is pretty premiscous.
 
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^ Which makes you wonder why no-one is isolating the optical isomers of MDA, keeping the more actibe R-isomer & methylating just the S-isomer to produce S-MDMA, which is the more active of MDMA's optical isomers. That way they could effectively double their output/profit as the less active isomers of both MDA & MDMA represent a waste of precursor, time, effort and money. For a bit more effort & only requiring one of the isomers of tartaric acid (if I remember correctly) to separate S-MDA from R-MDA, they could get so much more in return.

Fuck, I mean they could get optically active tartaric acid from even squeaky clean chemical firms without anybody raising an eyebrow! You'd think somebody would have noticed it considering it can effectively double profit/output (or are they doing too much of their own product, leaving them a bit befuddled when it comes to improving the business end? =D)
 
fab,

PIHKAL also states that racemic MDMA is the most qualitatively desirable.
As for the DOAM quote, it sounds great to me, almost like cannabis.
Personally, I prefer an ecstasy or cannabis high to say, DOC or LSD, except on the rare occasion when I want 5-HT2a agonism. CH3CH2OH gets into the CNS just fine.

One day, years ago, while delving deeply into the science library, I read a book that taught me the following. THC has a benzene ring with a
p-(n)-pentyl-2,6-dioxo(somethings)-C unit-C unit-sp2 hybridized atom.

This corresponds to psi-DOAM, with the (roughly) sp2 hybridized atom being -NH2.
And what do you know, Shulgin's description of DOAM sounds remarkably similar.

For example, smoking weed makes me "gay and voluble," it "in no way interferes with my day's activities," I eat "lunch" while stoned, and wierdly there is "a strange tenseness while driving."

I honestly believe that no RC company or whoever will be disappointed if they synth DOAM or 2CAM. As for 10mg being "not potent enough," I don't get it. That is 10x the potency of e and 30x the potency of mescaline.
 
You can't just make those sort of intuitive leaps considering there are several compounds from cannabis that contain a 3,5-dihydroxypentyl nucleus, yet have no CNS effects (and DOAM refers to the 2,5-oxygen atom distribution). The CNS effects of THC can be abolished by fully saturating the ring containing the double bond or making that ring fully aromatic. According to your theory it should still be active as it contains the 3,5 oxygen substitution pattern in the aromatic ring containging the pentyl group. In fact THC has one of the oxygens incorporated into a pyran ring and psychedelic CNS activity is removed if the pyran ring is opened .


Absolutely. But how would you know it's not being done?
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Seizures of drugs would come back as being optically active, but no reports say they are
 
I prefer S-MDMA to racemic MDMA. I'm not sure R-MDA is as qualitatively superior to racemic MDA though, even if it's more "potent" by weight. (What's potent mean anyway... 5-HT agonist activity? 5-HT release? Dopamine release?)
 
I've read a forum that was just people flaming at each other about which was better, d-meth, or the racemate. To each his or her own I suppose. One thing that I've noticed is that the combination chemicals such as MDA and MDMA are certainly more than the sum of their parts. 60 mg of either does nothing for me. 60 mg of each is better than 120 of one or the other. I still have to try 30 mg of MDE, MDA, MDMA and bk-MDMA in combination.
 
fastandbulbous said:
The CNS effects of THC can be abolished by fully saturating the ring containing the double bond or making that ring fully aromatic.
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HU-210 is a very potent derivative of THC, and both its hexahydro (fully saturated) and aromatic derivatives are more potent than HU-210 ifself.
 
Dr.Heckyll said:
HU-210 is a very potent derivative of THC, and both its hexahydro (fully saturated) and aromatic derivatives are more potent than HU-210 ifself.
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strictly what F&B says is true but only for THC and plain 1,1,dimethylheptyl derivatives of THC. oxidising THC to the aromatic Cannabinol CBN produces an essentially inactive compound as does reducing it to the fully saturated compound.
 
As helios was referring to DOAM and it's pentyl side chain similarity to THC, that's all I was concerning myself about (compounds with the 5 carbon side chain)

^How 'bout this combo?

10mg DOAM
10mg DOHX (...4-(n)-hexyl)
10mg DOHP (...4-(n)-heptyl)
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What about it? Once you get to 5-cabon chains and above pasra substituted to the amine side chain, it just starts getting too big for the hydrophobic 'pocket' of the 5HT2a receptor. Although I've never actually seen any wide ranging receptor affinity studies for DOAMompounds, I'm really pretty convinced that they're not going to have any significant interaction with either CB1 or CB2 purely because they are lacking so much more of the criteria for affinity to said receptors. If it was just down to a pentyl chain and two meta OH groups then olivetil (5-pentylrescorinol - a starting material for THC synthesis) would demonstrate activity at CB1/2 (and it doesn't)
 
fastandbulbous,
(remeber me from way back?)
That's not true. The 6 and 7 carbon chain analogues of THC are even more potent than THC itself is. DOHX and DOHP, though unsynthesized, will be likewise. That's my hypothesis here, anyway.

from PIHKAL: for psychedelics, keep the chain length short. for feel good compounds, use long tail lengths.
 
Helios. said:
fastandbulbous,
(remeber me from way back?)
That's not true. The 6 and 7 carbon chain analogues of THC are even more potent than THC itself is. DOHX and DOHP, though unsynthesized, will be likewise. That's my hypothesis here, anyway.

from PIHKAL: for psychedelics, keep the chain length short. for feel good compounds, use long tail lengths.
Click to expand...

I haven't looked at SAR of cannabinoids for a long time simply because they don't really interest me. but if I remember right, one of the requirements for a THC pyran type cannabinoid is that the long alkyl chain can bend into a hairpin type shape, this is why the 1,1 dimethyl heptyl analogues are more potent as they are more likely to bend into the desired hairpin shape. the dimethyl heptyls are a five carbon chain with the alpha alpha dimethyl. Ithought the plain straight chain heptyl is of reduced potency relative to THC, not my field so could easily be wrong though.

Also Most non-anandamide type ligands are have also two or more carbocyclic or heterocyclic rings carrying a H bond acceptor, para to the long alkyl. I guess that these interact with the same region on the receptor as the carboxylic group of anandamide, the natural ligand. DOHX has an isopropylamino para to the long alkyl dont think that will work.
As with everything, make it and taste it is the ony true way to know about 'DOHX' . its illegal here so couldn't be researched anyway.

I have never read of anandamide derivatives being used recreationally despite the fact that some of them are resistant to enzymatic degredation and work in rats.

when it comes to cannabinoids the only one that even slightly interests me is the water soluble morpholinobutyryloxy derivative of CP 55940, which should be similar potency to THC but orally active and with good bioavailibility by this route.

this seems to have veered way off topic sorry.
 
from PIHKAL: for psychedelics, keep the chain length short. for feel good compounds, use long tail lengths.
Click to expand...

Where does it say that in PIHKAL? I'm thinking it applies to the 4-alkylthio-3,5-dimethoxyphenethylamines, not 4-alkyl-2,5-dimethoxyPEA's/amphetamines. Nothing about DOAM gives even the slightest indication that it would interact with a cannabinoid receptor. I've stated all the reasons above, but if you don't believe me, then there's nothing else I can do to convince you otherwise other than to say get some DOAM & find out for yourself
 
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