I Like to Draw Pictures of Random Molecules

[Swerlz]

Shulgin did some research with deuterated 2c'd

The effects of 4-D and beta-D are similar to one-another, both as to dosage and effect. And with both, there is a close parallel to those reported from mescaline. It is reasonable to assume that the human body handles these materials in the same manner, although no metabolic studies have ever been published.

A similar deuterium substitution pattern is of course completely feasible with TMA and related 3,4,5-trimethoxy-substituted analogues. Some studies have supported the idea that the ability to remove methyl groups from such aromatic ethers might be correlated to endogenous schizophrenia. It is possible to imagine that, in such individuals, the effects of substituting trideuteromethyl groups for normal methyl groups might result in psychopharmacological differences of action. Two reports exist that describe metabolic products of mescaline that have lost this methyl group on the 4-position oxygen. It is possible that these might be produced in abnormal quantities in mentally ill subjects. There are also similar reports of the 3-methoxyl group being demethylated in man. Here, studies with 3,5-D (3,5-bis-trideuteromethoxy-4-methoxyphenethylamine) might reveal some differences in quantitative responses in man. These are extremely minor metabolites, however. I suspect that more extensive studies will establish that 4-D, 3,5-D and beta-D all have properties indistinguishable from one-another, at least in healthy subjects.

 

[JacksinPA]

Perhaps OT so please forgive me. I have both PIKHAL & TIKHAL & actually met Shulgin at an ACS meeting in Anahaim, CA. Nice guy. Would have enjoyed talking to him longer. Believe he started out as a research chemist at Dow Chemical's former ag research facility in Walnut Creek, CA. I think he created DOM there in 1963. Dow was more interested in making Agent Orange for the Vietnam War.

 

[JacksinPA]

In the middle to this nasty flu epidemic, I have 10 75 mg caps of generic Tamiflu sitting in my fridge at 37 deg. If I don't need it this year it should be OK for use next year. I would never think to store this kind of molecule at room temperature.

 

[JacksinPA]

SAR studies have shown that reversing the position of the carbonyl & amide nitrogen groups produces so-called retro-anandamides with more potent receptor binding affinity.

 

[JacksinPA]

SAR studies have produced other more potent anandamide derivatives such as ACPA where the ethanolamine function is replaced with a cyclopropyl amine group:

The 4 cis double bonds are required for full activity.

 

[JacksinPA]

I've been taking gabapentin for years to treat the depression side of bipolar. At 100-200 mg 2-3 times/day, it's like taking sugar pills - no noticeable effects. But when I tried 2,000 mg in one shot on a mostly empty stomach, I had quite the pleasant buzz that evening.

There's a discussion on the Gabapentin High thread about this drug's bioavailability & absorption limits. That got me thinking about this molecule. Basically it is an amino acid with a big, fatty cyclohexane ring in its middle. This type of molecule is called zwitterionic as it contains both an acidic & a basic functional group. That got me thinking about simple water-soluble acidic & basic salt derivatives that might significantly alter the drug's effects. The acid form could be the hydrochloride salt & the basic form could be the sodium salt. Both of these are known materials. See graphic:

 

[sekio]

Gabapentin is kid of weird in that it's not absorbed through "normal" diffusion, it actually uses the amino acid transporter to cross the BBB. Staggered dosing is much more effective than bolus dosing - BA goes down with increasing dosage.

Forming a salt of either kind is not really useful - the blood has a fixed pH of around 7.4, the stomach has a fixed pH of approx. 1-2, and the intestines have a pH of about 6-7.

So any orally absorbed drugs will likely exist as a HCl salt in the stomach and only later on, in the intestine, do they change to uncharged forms which cross lipid membranes easier.

There has been a prodrug with much higher BA which releases gabapentin upon metabolic hydrolysis, called gabapentin enacarbil. Note the bulky group blocking the ionizable NH2 present in gabapentin.

 

[JacksinPA]

It's hard to believe that you apparently can buy this plant material on the internet. https://www.uspharmacist.com/article/the-dea-changes-its-mind-on-kratom

I created these structures out of curiosity as I had not been familiar with Kratom until just now. I also was challenging ChemDraw's Name > Structure function. There are some differences between the structures of the parent alkaloid & its 7-hydroxy derivative.

Interesting reading about the pharmacology of these alkaloids.

I was just over on the Kratom thread & I wouldn't touch this stuff unless somehow my life depended on it.

 

[Nagelfar]

It's hard to believe that you apparently can buy this plant material on the internet. ....I had not been familiar with Kratom until just now...I wouldn't touch this stuff unless somehow my life depended on it.

Kratom is quite widely abused, in my somewhat smaller-ish American town there are signs at headshops with just one word "Kratom", and people everywhere around have been using it for going on a decade or more. Not really at all considered unsafe, unless you consider opioid addiction in all its forms so.

 

[JacksinPA]

I was reading some of the withdrawal stories in the Kratom thread & it sounds like trying to get off heroin. I have an addictive personality but no interest in even experimenting with something that really gets the hook in you. I'll stick to my prescription benzo, gabapentin & Polish potato vodka, thanks!

I have had fun with the usual recreational drugs like Cannabis, Psilocybe, LSD, nitrous oxide, gabapentin, organic mescaline, & Polish potato vodka. But I have never felt the need to get involved with anything that involves physical addiction & the specter of having to go through withdrawal. I'm a senior citizen & my doctor keeps me on a pretty short leash, so getting hooked on something like Kratom does not sound like a good idea.

 

[JacksinPA]

From another thread:

 

[sekio]

something that really gets the hook in you

I suggest you read a couple stories of benzo withdrawal

 

[JacksinPA]

My DO is very happy prescribing alprazolam to me & I'm very happy using it to fall asleep after getting up to pee in the middle of the night. Why no tolerance to this after 35+ years is a mystery to me as I know I've developed tolerance to flurazepam & possibly to midazolam & fentanyl as well. Propofol is now my anesthetic of choice for anything surgical. Have used it twice in the last 18 months with very good results.

Strange about the fentanyl as I've only had it used on me (cataract surgery) twice & both times it instantly knocked me out. But a mixture of midazolam & fentanyl that they were giving me via IV during an endoscopy didn't even give me a buzz. I've had midazolam 5-6 times for colonoscopies & woke up only once when this big GI doc was poking into me hard with the 'scope, then went back to retrograde land.

While I'm aware that discontinuing even low regular doses of benzos can cause seizures & possible brain damage, I'm just glad that tolerance hasn't shown up & I can continue taking them.

Besides the lack of tolerance question, I find the fact than alprazolam rapidly puts you into REM sleep very interesting.

 

[Solipsis]

The problem only gets serious if you have reasons to use these sorts of drugs daily to (self-)medicate a persistent problem. Benzo's are so much worse than kratom in this respect and can be at least as bad or worse than serious opioids if you feel very inclined to use daily.
Just like with incidental benzo use, incidental kratom use is fine if you are relatively stable and problem-free. This is your major predisposition to addiction, not just the lack of self-control people associate with addiction. Coming off opioids feels hard and horrible but with benzo's it can feel functionally impossible especially because it can take so incredibly long to function ok again.

Opinions on kratom seem quite polarized, some people are suprisingly scared of it and others find it unreasonably harmless in all respects. The truth is somewhere in the middle, there are some positives like the ceiling effect limiting but not eliminating abuse potential. It also means people don't die but just feel like shit if they take a lot... unlike with heroin and other opiates where ultimately both of those things happen.
I know people have serious problems with chronic daily use of kratom... I can personally start to like it a bit too much when still finishing a first small batch every once in a while and don't like it to quit again but I manage and just quit it again anyway whereas I wouldn't dare with harder opioids anymore since I had problems with them. There are just a bit too many off feeling sides to kratom for me to really be okay with taking it for extremely long periods.
There are also signs that kratom does not stimulate the pleasure centers in the brain quite like morphine etc do.

It's a personal thing and not a black and white story. By all means if you are worried, avoid certain drugs to be sure... seems preferable over making an unnecessary and grave mistake.

I do like benzo's such as alprazolam or etizolam for sleep even though they are not hypnotics. The more hypnotic benzos are the more you go out like a light but the worse it also seems to be for your actual sleep quality. I think way too many elderly seem to be on drugs like these and they were a nightmare for me to take regularly (but I can safely take them only sporadically now), on the other hand I understand completely the reasons like pain and discomfort to treat... I just dread the moment I would have to constantly treat such symptoms that way, things get so lopsided it is an irreversible proces.
Benzos don't have as bad a name as many other drugs and you might not think this from just taking one every once in a while but trust me: they can be among the worst.

Anaesthetics are a different story entirely. Some can be really heavy, and such a rapid route of administration of anaesthetic doses of the drugs you mentioned leave you little time to get into a 'recreational phase'. The seizures etc can happen with just alprazolam or etizolam but typically you would need to take rather high dosages and/or quit abruptly which are both terrible anyway. I can't imagine what it is like to abuse things like propofol etc.

 

[Soulfake]

Some benzo analogues I'd like to test and a random phenethylamine-norbornane compound. I wonder why there are no methoxy-substituted benzos? Also I'm interested in the pyridine-analogues like Bromazepam and Pyrazolam as well as 3-methyl benzos like Meclonazepam, why are those so rare?
/edit the second one is Diazepam for comparison

 

[Solipsis]

Isn't the planar structure of phenethylamines pretty important?

I wonder why 1-methyl benzos are not more available.. @ 3-methyls: meclonazepam is kinda nice but nothing special I guess - haven't tried high dosages and I am not really looking for that anyway, it was suspiciously cheap when i bought it and just served as a backup. I guess it didn't meet therapeutic standards in trials, which I would understand if only because it has little to contribute that other benzos don't do better.
It also has a chiral center there which isn't exactly something you want or need either unless it's *that* potent right?

 

[roi]

Cyclopropylpemoline appeared as "nootropic" a while ago, this might increase fun & potency.

 

[JacksinPA]

You have the structure wrong for this molecule. See https://psychonautwiki.org/wiki/Cyclazodone. You've drawn it with the side group as oxetan-3-amine rather than cyclopropyl amine. It's also said to be hepatotoxic. Here is the correct structure for cyclazodone:

I did a brief Google search & see it available as a 'research chemical'. Caveat emptor.

 

[aspiringdrugdesign]

Currently going over organometallics rn, I'm aware this would probably have genotoxic / other toxic properties, but can anyone tell me what dangers would arise from something like this?

I was thinking the Br would leave the magnesium pretty easily, which could brominate things that shouldn't be brominated. Is there more to it?

 

[JacksinPA]

What you've drawn is called a Grignard Reagent. Firstly, it couldn't exist as you've drawn it because the Ar-Mg-Br would react with the free amine on the end of the ethyl chain. I don't believe this would act as a brominating reagent even if you protected that amine first with groups that could be removed in a later step, like benzyl groups with can be removed via hydrogenation. I'm not familiar with any application of these reagents as brominating agents. There are simple, commercially available molecules like N-bromosuccinimide & even elemental bromine for doing that.

Grignard reagents are formed in solution of either dry ether or tetrahydrofuran & are not usually isolated but are reacted directly with things like ketones & aldehydes. With metal catalysis they can be made to couple with things like alkyl halides.

So yes, there is a lot more to it. Just being able to draw a structure doesn't mean it makes sense or can be made or exist in the real world.

I don't know what your educational background is in organic chemistry, but Grignard chemistry is usually first-year college organic 101. If you haven't already, order a good introductory organic textbook from Amazon or your local college bookstore. Or just read this: https://en.wikipedia.org/wiki/Grignard_reaction

Whatever you wind up doing, be very careful with Grignard chemistry. You're working with volatile & flammable solvents that have to be specially purified to remove peroxides & dried before using. The Grignard reaction itself, where magnesium metal reacts with the organic halide, are many times difficult to get started due to factors such as surface oxidation on the magnesium metal you are using. And once started, they can get pretty active, so you have to work under efficient reflux condensers for proper cooling. And most Grignard reactions are run under a continuous flow of dry nitrogen. Good luck!