Dissociatives The Big and Dandy 3-MeO-2-oxo-PCPr (MXPr) Thread

[SpiralusSancti]

It’s either (practically) 50% – 50% or (practically) 100%, hardly with any substance you’ll end in between without mixing.

And guess what, actually there is example of a drug that works only when crystallizes in one form, it’s counterintuitive to expect that to be case with anything as you say, it should be the same after it dissolves. Substance I mention is either HIV or cancer medicine, can’t remember and I’m too lazy to look it up now.

 

[bene79]

It’s either (practically) 50% – 50% or (practically) 100%, hardly with any substance you’ll end in between without mixing.

And guess what, actually there is example of a drug that works only when crystallizes in one form, it’s counterintuitive to expect that to be case with anything as you say, it should be the same after it dissolves. Substance I mention is either HIV or cancer medicine, can’t remember and I’m too lazy to look it up now.

it's a bummer you're too lazy to look it up because it sounds really interesting.

 

[bene79]

Also I disagree with what you said about it being either ~50:50 or ~100. It really does depend on the synthesis. Some types of resolutions won't give %ee of 100 right away.

 

[Img_9999]

I think there might be something to the polymorphism theory that has been previously discussed in various of the ACHA big and dandies. I haven't looked deeply into it, but it seems that crystal polymorphism is specially important in determining the bioavailability of poorly water soluble drugs. Most ACHAs are indeed rather hydrophobic. Apparently some crystal forms enable for better solvation of the molecules, affecting absorption kinetics and/or improving bioavailability.

Here's an example of a paper discussing this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331817/

If we consider that the effect profile of ACHAs seems to be vary wildly with different ROAs, I guess we can assume that absorption kinetics significantly impact the subjective effects precieved when ingesting them. So in theory, differences in crystal structure, which as said above can impact absorption and bioavailability, could be expected to cause differences in subjective experience.

I need to take a closer look at all of this in some point, though. I know a fair bit about protein crystals, but close to nothing about crystallization of smaller molecules : D

 

[bene79]

I think there might be something to the polymorphism theory that has been previously discussed in various of the ACHA big and dandies. I haven't looked deeply into it, but it seems that crystal polymorphism is specially important in determining the bioavailability of poorly water soluble drugs. Most ACHAs are indeed rather hydrophobic. Apparently some crystal forms enable for better solvation of the molecules, affecting absorption kinetics and/or improving bioavailability.

Here's an example of a paper discussing this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331817/

If we consider that the effect profile of ACHAs seems to be vary wildly with different ROAs, I guess we can assume that absorption kinetics significantly impact the subjective effects precieved when ingesting them. So in theory, differences in crystal structure, which as said above can impact absorption and bioavailability, could be expected to cause differences in subjective experience.

I need to take a closer look at all of this in some point, though. I know a fair bit about protein crystals, but close to nothing about crystallization of smaller molecules : D

Interesting. But I think (and I might be wrong) that these kind of drugs are usually sold in the salt form (highly polar -> soluble) rather than as free base (unpolar/hydrophobic -> poorly soluble).
you can check it by trying to dissolve some in water. I never tried MXPr, but my DMXE dissolve like it was nothing. Obviously, in solution there's no crystal structure and the whole argument becomes irelevant. Also, at least when taken orally - the freebase form should quickly react with the HCl in our stomach to make the salt form.

In any case, even when your substance isn't soluble in water (which I don't think is likely) - you can easily solve this problem by first dissolving your powder in a bit of ethanol and than drinking it (considering the dosage is really low, I don't think you'll need more than a few milliliters). It can be a nice experiment for those who have two batches of the same compound that differ in effects.

P.S. I completely agree with your logic right here: "I guess we can assume that absorption kinetics significantly impact the subjective effects perceived when ingesting them. So in theory, ... differences in absorption and bioavailability, could be expected to cause differences in subjective experience.". I also suspect that a similar principle might be the reason why people swear to distinguish between different prodrugs of LSD.

 

[Img_9999]

Interesting. But I think (and I might be wrong) that these kind of drugs are usually sold in the salt form (highly polar -> soluble) rather than as free base (unpolar/hydrophobic -> poorly soluble).
you can check it by trying to dissolve some in water. I never tried MXPr, but my DMXE dissolve like it was nothing. Obviously, in solution there's no crystal structure and the whole argument becomes irelevant. Also, at least when taken orally - the freebase form should quickly react with the HCl in our stomach to make the salt form.

In any case, even when your substance isn't soluble in water (which I don't think is likely) - you can easily solve this problem by first dissolving your powder in a bit of ethanol and than drinking it (considering the dosage is really low, I don't think you'll need more than a few milliliters). It can be a nice experiment for those who have two batches of the same compound that differ in effects.

P.S. I completely agree with your logic right here: "I guess we can assume that absorption kinetics significantly impact the subjective effects perceived when ingesting them. So in theory, ... differences in absorption and bioavailability, could be expected to cause differences in subjective experience.". I also suspect that a similar principle might be the reason why people swear to distinguish between different prodrugs of LSD.

Yeah, you ate right, most ACHAs are available se HCl salts, so they should be readily dissolved anyway... I've still found that some of them are kinda hard to put into solution. I wonder if cocrystals can also display allotropism, would have to look into that but not now.

I like your suggestion though, about previosly dissolving the dissos in water or water + ethanol and then compraring differences un effects. Its a simple experiment that could give some hints on the matter.

I've also come to the same conclusion regarding prodrugs, absorption kinetics color the experiences for sure in that case. Just look at the difference between morphine, codeine and heroin.

 

[Pastel]

I still have MXE from 2011 in my collection of disassociates from that period, but I kept putting off ordering DMXE, FXE, HXE, MXiR and MXPr until the last store serving US shut its doors at the demise of LL. It sucks. I console myself with a thought that had I ordered them, it would probably have taken me years to get to try them.