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2-methylamino-1-(2,5-dimethoxyphenyl)propan-1-one

Theres no way of overlapping the two structures so that things like lone pairs and double bonds etc (all the areas of charge sparation in molecules that allow binding to the receptor protein through electrostatic attraction) are positioned in the same way in space, which is fairly important in ability to bind to receptor proteins. About the only way you could get something containing a 2-aminopropyl group to interact with the CB1 receptor, is by replace the n-pentyl chain with a 2-aminopropyl group (CBVD is the analogue with an n-propyl chain in the place of the n-pentyl chain, and is thought to contribute to the heady high of Thai strain plants). This definitly won't fit in the 5HT2a receptor though - it's got too much bulk attached to the benzene ring
 
Not to be rude, but...

Some people like to think inductively and some people like to think deductively. I like to think in whichever model solves the problem at hand.

I can overlap any two structures I want, whether the resulting hybrid will be psychoactive is what is being tested. Sometimes it works, sometimes it doesn't. I can theorize why it did or did not work, and so can you, but neither one of us really knows and neither does it make any difference. The psychoactivity or lack thereof simply exists or it does not.

Science cannot exist without experimentation, and good experiments are based on good and/or lucky hypotheses. As Shulgin wrote something to the effect of, "logic doesn't have anything to do with novel drug synthesis."

The much hailed computerized structure activity relationships have been miserable failures at predicting new effective drugs. High throughput screening is not fairing much better, and big pharma is starting to feel the heat from shareholders.

For example, I can overlap the structures of MDA and dopamine if I know to cap off the hydrophilic hydroxyls with a carbon to cross the blood-brain barrier and to add an alpha methyl carbon to inhibit the body's monoamine oxidase inhibitor system. This is somewhat of a trial and error process, but evolution has done all of these experiments for us already and low and behold there is all-natural safrole, all-natural pot, all-natural cocaine, all-natural DMT containing plants, ma huang, shrooms, mescalinic cacti and opium.

Sure, safrole has to be aminated to become truly magical, but this is a small step when compared with coming up with an entirely novel drug from scratch. Also, comparing the structure of all-natural Chinese ephedrine with safrole will lead one in the right direction.

Or I can overlap the structure of psilocin with serotonin if I shift one aromatic hydroxyl group over a few degrees, and get an active compound.

I can find a 3,4-dioxygenatedphenylethylamine skeleton in opium based narcotics. I can overlap the structure of amphetamine onto fentanyl in the obvious place (to me) and make it much more potent than it already was; the resulting compound is called 3-methylfentanyl. Likewise, I could add a 3,4-methylenedioxy bridge onto the phenyl ring of fentanyl and who knows what would happen.

I can overlap gamma-aminobutyric acid with gamma-hydroxybutryric acid (a shift from an amine to an oxygen) and get a psychoactive product.

In fact, and I apologize for ranting a tad, but I saw a beautiful example of the natural product to semi-synthetic natural product drug design last night on Google while doing a search nicotine analogues isolated from certain frog species. The isolated the analogue and then tinkered with it 500 times, producing a semi-synthetic pain reliever 200x more potent than morphine.

And guess what?, it's called ABT-549 or some random shit, but the molecule structure consists of a nitrogen with 3 carbons in a ring (an azetidine ring) and an oxygen attached to the carbon alpha to the nitrogen. The oxygen itself is attached to a pyridine ring with a chlorine ortho to the pyridine's own nitrogen.

Anyway, look up the structure yourself and you will see spectacular similarities to the phenylethylamine world. Call it the aromaticoxycarbonitrogen family, but this drug clearly fits the same binding site as the PEAs such as meth and mdma, and I think I would be interested in hearing some trip reports on it.

Interestingly, the company that has done all this research with it is being very tight lipped about how the clinical trials have gone, and one website even went so far as to say that whether this research chemical is addictive or not is unknown. Yeah, I bet it is.

Better living through alchemy and the judicious application of Ockam's razor.
 
If you look at all the paper by Dave Nichols, he's gone a step past Shulgins work with the phenethylamine hallucinogens, pinning down the structural aspects that alter the SAR for drugs that interact with the 5HT2a receptor. By analysing the 3D structure of the protein that forms the receptor, it's possible to know where all the main hydrogen bonds and other electrostatic charges are, and the complimentary charges on the various ligands.

Of course they do receptor modelling for receptors that they know the structure of, that why Dave Nichols has made whole series of variations on the classic hallucinogenic groups. The whole aspect of receptor modelling has produced diferent series of drugs , where only one aspect of receptor binding is studied (such as the variation of the diethylamide group of LSD). In that way they determine the optimum ligand, step by step. If you have a look at those papers, you'd understand why things like DOAM don't have any chance of interacting with the 5HT2a receptor, also why all of the steric bulk attached to the benzene ring in the THC molecule would prevent it getting anywhere near.

I end up suggesting a possible series of potent 5HT2a agonists, but as for how drugs interact with the receptor, it's just pulling the theme of a couple of different studies together. Link is here
 
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I used to have lengthy, multiple, involved email questions and arguments with Dr. Dave until we got sick of each other. Dave Nichols is can be a cranky old professor when he wants, but he seemed pretty nice on computer anyway.

What makes you assume I am looking for a 5-HT2a agonist at all or that I said DOAM was one? DOAM may not be a 5-HT2a agonist, but its effects are described by Shulgin in "PiHKAL" (Dr. Dave derisively called "PiHKAL" devotees, "Shulgin-worshippers") as something to the effect of "This developed into a pleasant high that in no way interefered with my day's activities" and "I was quite gay and voluble at lunch" and "There was a strange tenseness during driving." All that at only 10 mg; what about 100 mg?

PM me and send me 100 mg DOAM and I'll tell you. It's got to be better than 100 mg doses of TMA-2 and TMA-6 were for me. It could even rival MDMA and be much more psychedelic as well. As for the lipophilicity of the added 4-(n)-pentyl group, there can be no argument against its extreme affinity for the brain's phosphatidyl nucleotidlyl triacylglycerides and proton pumps (all imaginary biological pseudoscientific adjectives to explain the unexplainable "Meaning of Life)."

I am not interested in the pure biological systems upholding the metabolism and effects of drugs, but rather the organic chemical structure of the drug itself, along with its density, color, refractive index, odor and taste. If you think computerized model, even done with supercomputers, can approximate what kind of molecular interactions a drug will have with target and peripheral proteins as it makes its way through the human body, then you should work for IBM.

According to the Hindus, the meaning of life is an Indian word called LILA that, roughly translated, means 'God's play'--namely, the lives of you and me are the soap opera of God and the demi-Gods and host of angels who support him.

Speaking of far out religions, I wonder how Bob Dobbs' church is doing in 2004 or if it is still doing? The mastercreator behind Church of Bob Dobbs always reminded me of the Hive's Strike in his mindset. One of those books even described the chemical composition of a fictitious, ideal planet; its air consisted of 10% percoset (oxycodone) and 90% MDMA. My perfect planet would have 15% THC, 25% Zyprexa, 25% pure meth, 5% Valium, 5% cocaine, 15% MDMA and 10% hydrocodone. Ananda!!!

I know White Fluff reportedly inadvertently, I presume, killed himself in a massive drug overdose of one kind or another. I heard that last factoid 2nd hand at the hive, but it's probably true because I haven't seen any 300 microgram family blotter coming down from Tennessee in several years. BTW Billy / "Freeze" from Tennessee who was friends with Dawn if you or one of your friends sees this message, then PM me for sure, and we will hang out.

I had some "Mad Hatter" from up in the Appalachian foothills and mountains once, but while very strong it was no match for the clean, sunlight bathed glow of "White Fluff."

Chinacat, a member at certain other message boards and maybe this one too, ranked "White Fluff" as the highest grade of about 3 or 4 grades of commercial acid and family acid which she had trafficked for years at the Grateful Dead shows while in her mind being protected by God by not being ever detained or arrested by the authorities for the technically felonious LSD distribution.

As for the current US LSD drought, never fear, the Dutch scientists got good enough to synth LSD all by themselves and supply the world with billions of MDMA/MDA/MDE/METH pills that it requires seemingly every weekend. Unfortunately, the Hollander that I talked too wanted 500 USD per sheet. Supply, demand and the vagaries of commondities on the world market is mind boggling, but I never paid more for 175 USD for family vials or commercial white blotter either.

Alternatives to LSD:

Luckily, 4-OH-MIPT can be dissolved in ethyl alcohol in sweet breath bottles and ingested 35 to 40 mg at a time (do you math; remember mass, m (in kg), equals volume (in m3) times density (in kg/m3, for example)). The 4-OH's react with each other to form purple dimerized peroxides which color the solution black to dark purple. Side effects include a mild high, few visuals, moderate duration (from 15 min to kick in to 5 hours to wear off or at least significantly subside in intensity), some euphoria, some music enhancement, increase in friendliness, mild headache, increased color appreciation and facial flushing.

fastandbulbous,

If you are a 5-HT2A agonist purist scientists poppin' Guiness, then I would suggest devoting your life to lsd manufacture for a while. Only the people with pure karma withstand the initiatory "thumbprint," while the actual chemists often say a prayer to bless the recipients of each of the users of their new batch of crystal, and get high by osmosis.

Personally, I like the way the word 'crystal' can refer to pure lsd or pure methamphetamine ("ice"), even though they are as different from each other as night and day, literally. I like to think of shards coming from the frozen tundra of Alaska and northern Canada where the Northern Lights (an obvious double reference there) appear repeatedly and where pot is a misdemeanor at most, while LSD is a dirty, sweaty, insane Australian / South Pole aboriginal type. These two crystals are the primordial serotonin and the primordial dopamine crystal vibrations and blueprint for consciousness in what would otherwise be a large group of non-sentient, silly simians (note the alliteration or was that consonance?).

Anyway, one time when I was locked up in a state run mental institution this middle aged Jewish man from NY told me that I looked like the picture of Roget of Roget's Thesaurus fame. And my vocabulary does tend to border on the ponderous side--I used to memorize extensive word lists; now I read medical dictionaries. We don't look alike, as it turns out, but then my sister's father-in-law told me I look like Abraham Lincoln, which I kind of do, at her June wedding. He looks like Thomas Jefferson, though; alas, if only Jefferson in all his knowledge and wisdom had added an amendment to the Constitiution with the Bill of Rights (the first 10 amendments of the Constitution) prohibiting the US government's banning of any food or drug.

This Christmas someone needs to come up with a cannabis effect producing amphetamine and then a nicotinic amphetamine as well. I wouldn't mind doing a phat rail of crushed up shards, too.

Important Factoid:

Did you know that under the federal sentencing guide lines you can have up to 5 grams of pure meth before getting the automatic 5 years with only 15% of the time eligible for parole?

"I'm down here on my knees, I'm saying please, pleassee."--Edward KaSpel of the Tear Garden (also sings the lyric, "for the pill, the precious pill").

Finally, and I apologize for rambling, but as for 1-(2,5-dimethoxyphenyl)-2-methylaminopropan-1-one hydrochloride, that shit is crap and should not be purchased. I finally chose to flush my last 750 mg of it down the toilet; that's all it was worth. Icould have PM'ed one of you and sold it for cheap, but I didn't. Drug dealing, even with RCs, is a sketchy business which I avoid. Cheers.
 
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joystick said:
Alternatives to LSD:

Luckily, 4-OH-MIPT can be dissolved in ethyl alcohol in sweet breath bottles and ingested 35 to 40 mg at a time (do you math; remember mass, m (in kg), equals volume (in m3) times density (in kg/m3, for example)). The 4-OH's react with each other to form purple dimerized peroxides which color the solution black to dark purple. Side effects include a mild high, few visuals, moderate duration (from 15 min to kick in to 5 hours to wear off or at least significantly subside in intensity), some euphoria, some music enhancement, increase in friendliness, mild headache, increased color appreciation and facial flushing.

First I would like to thank you and Fastandbulbous for your very informative posts.

In the spirit of harm reduction I would just like to add that...


In my experience 4-HO-MiPT is effective in the 15-20mg range. I've taken larger doses before, but it seems that myself and most other people I've talked to are comfortable with 20mg for a full dose.

Duration seems to be somewhat dose dependant. 10-15mg usually lasts around 4-6 hours. 15-20mg usually lasts around 6-8 hours.

Reported negative side effects are:
> Nausea / vomiting (uncommon, increases with higher dosages).
> Diarrhea (more common for people who have this problem with other tryptamines).
> Gas / burping / bloating.
> Pupil dilation.
> Feeling of having a "lump in your throat."
> Increased body temperature / feeling warm or hot.
> Headache (uncommon, usually happens after the come-down).
> Trembling / shaking (uncommon, similar to what many people get on 4-HO-DET and 4-HO-DiPT, but much less severe).
> Feeling of having to urinate frequently, but you may not be able to.
> Jaw clenching.
 
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Don't stop taking the lithium, but I think you need more

(I recognise the "bipolar" style. As the saying goes,"it takes one, to know one", and I'm no stranger to subject continuity and hypomania)

"logic doesn't have anything to do with novel drug synthesis." .

If it's from PIHKAL, that statement is 30 years old (drug design is light years away from what it was in the mid 70's), besides, Shulgin is primarily an organic chemist who got interested in psychedelics, not a pharmacologist. Although they may be dealing with the same class of drugs, their background heavily colours what they see in terms of SAR studies.

And on a final note, the OH groups on THC are orientated meta to each other on the ring, but para in the case of DOAM. The only thing they really have in common is that they're both controlled drugs
 
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perdonname, amigo

fastandbulbous,

Thank you for pointing out to me and the world that I am crazy and should be taking more anti-psychotic medications, but yes, I will admit that I am at least somewhat hypomanic right now, to say the least, but I am meticulously and competently adjusting my affect's amplitutude and ambiance so as to be just as "normal" as any other man with a microsized penis and a truly near genius IQ, two of life's little "Double Whammies," as Felicia would say. Anyway, to deflate my mania and sleep as necessary I am presently taking Valium and Zyprexa, prn. Lithium gives me cognitive impairment, amotivation, trembling hands and flat affect. I simply must use certain substances necessary for me to achieve the burst of positive motivion into one's life that energizes to do what must me done with one's life, if need be. Otherwise, let it be, but any Zyprexa or Clozaril patient, or patients under the influence of any of the other, new, expensive atypical antipsychotics which block both D2 and 5-HT2a receptors with few side effects save for weight gain and shortness of extra spending money. Anyway, it's time to party so have a ball. As it turns out this penultimate sentence of this paragraph represents a too long drawn out, half sentence and should be disregarded. If you choose to correctly complete it, insert the sentiment induced by the following words: [those crazy people] shoud be allowed to take amphetamines to counteract their powerful DA and 5-HT blockers.

"You gotta fight for your right to party!"--The Beastie Boys
"Tonight I'm tired of dancing all by myself, tonight I want to dance with someone else!"--Lady Madonna (which I did last night, actually, with an attractive enough girl with much drive and ambition, a nice Honda, and a good job at MCG. I may become a physician as of yet in the end certainly and judge too. As one judge said to another, "Be just. And if you can't be just, be arbitrary." Even better, she recognized the obscure breakbeat song lyrics I qouted her and she only had one chance. Actually, having a high IQ is good sometimes.

Goodbye, I love all of you readers with God's passion minus 777.
Analyze the linguo-religio implications of the Spanish phrase, "Hey, Zeus?"
"Let's get higher."--Naan Commercial Hits

The best thing about this new girl is that she, like me, has the Sun in the constellation of Leo. I will do her comprehensive astrolgical chart shortly, God Willing.

"Get down to my technique,
Like a superfreak.
I want to see you jam
At my command."--DJ Tripnotic, "Electrified Acid"

Florida Breaks Rock.
My DJ name is DJ Sunlight.

"Well, if that's your name, then you must be from Heaven."--Yana

"(smiles) Yes, Yana, I am from heaven."--amp

"Now, who's the real Doogie?"--The Notorius Biggie Smalls

I'll shut up now, forgive me, but let me add that cats have 9 lives and before being judge or physician I will be both a farmer, a homeless person, a tour kid, an insurance salesman, and an ecrivain, to use the French Canadian colloquiallism. Also, bear in mind that if you did as many good drugs as I have you would love to type long monologues for free on the computer every day too.
People sometimes almost want to feel sorry for me, but not usually.
 
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300mg of this shit was consumed last saturday.

absolutley nothing happened.

i wonder if there is an easy way to brominate it? *goes and learns chemistry*
 
Convert your HCl salt to the freebase and brominate with Br2 in acetic acid. See PiHKAL under 2-bromo-4,5-MDA, I believe, and substitute your RC for MDA. Even then, this compound just looks more and more worthless. I finally flushed my last 750 mg down the toilet, and I'm not sorry.
 
joystick said:
Convert your HCl salt to the freebase and brominate with Br2 in acetic acid. See PiHKAL under 2-bromo-4,5-MDA, I believe, and substitute your RC for MDA. Even then, this compound just looks more and more worthless. I finally flushed my last 750 mg down the toilet, and I'm not sorry.

really? i was about to do that and then thought.. "hmmm if i was to brominate it i'd end up with the cathinone version of DOB, wouldnt i?"

that might be interesting :) i've always wanted to try DOB and DOM ... i like 3 day trips and im sick of consuming 5-8 blotters in a night, keep getting paper stuck in my teeth :D

but i'll never do this because i wouldnt have a clue how to get Br2 and its prolly scheduled or watched anyways.
 
Or you could use I2. But does the carbonyl have to be protected, that is the question... I'll dig up my chem book if no one knows

-ek
 
If I'm not mistaken, brominating this chemical would yield the beta-ketone of N-methyl-DOB.
 
Sorry, yes, the carbonyl would have to be protected with ethylene glycol (the main ingredient of antifreeze; chemical formula HO-CH2CH2-OH) before bromination of the phenyl ring. Then it would have to be deprotected to get the benzylic carbonyl back. At this point you would have the methcathinone analogue of DOB.

To get the N-methylamphetamine analogue of DOB, one could then reduce the carbonyl via the Wolff-Kishner reaction which uses hydrazine and KOH to reduce ketones (R-C(O)-R') to alkanes (R-CH2-R') in one step. Hydrazine is a very dangerous chemical to work with, but Br2 is fairly common and almost certainly not a watched chemical--any more so than any other lab chemical anyway.

Alternatively, 1-(2,5-dimethoxyphenyl)-2-methylaminopropan-1-one HCl could be reduced with sodium borohydride (NaBH4) to the pseudoephedrine analogue of 2,5-DMMA and then reduced with red P and iodine to N-methyl-2,5-DMA. This compound could then be brominated to yield N-methyl-DOB.

I don't believe N-methyl-DOB has an entry in PiHKAL, but I do recall mention being made of N-methyl-DOM, which was rated less favorably by Shulgin than DOM itself.
 
We're not here to help you synth up drugs. There is a lot of good info out there, but synthesis discussion is not allowed in here. --SKL
 
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Wow, there is a whole lot of bullshit in here, I'd better bring my shovel. First off, I think that it is always a good idea to start low and build slowly (read very slowly) when dealing with a novel chemical. I certainly would always want to screen for idiosyncratic responses before I jumped in head first. Second, since 2,5-DMA is not particularly active and no N-substituted phenethylamine has proven to be a potent psychedelic, I think this 2,5-dimethoxy-methylcathinone compound was doomed to inactivity a priori. And finally, having some bipolar tendencies myself (Type II, for what it is worth) and knowing some rediculously bipolar people, I will say: this is what happens when we just stop taking our mood-stabilizers...logorrehea (diarrhea of the mouth) and the general spewing of copious bullshit.
 
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