The Large and Nifty Not-quite-advanced Drug Chemistry, Pharmacology and More Thread

[pharmakos]

Well, you also need reference compounds of relatively high purity for a TLC analysis to work properly. I agree that TLC analysis would be a bit too complicated for the average raver.

with enough standardization i don't think the end user would need high purity reference compounds

 

[skillet]

Maybe not high purity, but I'd have thought you need some sort of reference. I guess Rf depends somewhat on moisture content of the silica (or whatever), particle size, maybe temperature, solvent saturation of the chamber atmosphere, and maybe some other stuff?

 

[Iodjini_dk]

^^Thats why one cannot always rely on Rf values alone. A stated Rf value in a given solvent only provides an interval of some sort. It can vary as much as 0.3 IME. But maybe a device could be made that controls some of these factors as solvent saturation, chamber atmosphere etc. Sounds a bit expensive though
The reason for high purity reference compounds is that even minor impurities can give rise to big spots in a TLC analysis. I dont know for sure but I could imagine that the average street drugs give rise to numerous spots in a TLC analysis as they are rarely purified.

 

[A Lucid Pet]

I guess this would probably go here before it got it's own thread. Kinda caught between Cannabis discussion and ADD here.

Well I was making some canna-butter by boiling a little over a pound of butter, water and plant material in a pot for about an hour. I was going to strain this mixture and let it cool so the butter would coagulate and separate from the water. At the last second I decided to use a pitcher to pour the mixture into the filter and washed it out really quick with palmolive dish soap. Apparently I didn't rinse it out as well as I had thought.

Upon pouring the mixture into the pitcher I noticed the soap bubbles but didn't really think much of it. When I make butter I usually put ice in the solution to hasten the cooling of the butter-water solution. Right away I could see that the remaining soap was not going to let the butter coagulate properly because of it's ant-grease properties (whatever those may be lol).
I tried to skim the butter off of the top of this solution and put it over ice in a bowl and put it in the freezer hoping I could just separate the ice from the frozen butter easily and then make some soapy cookies. The ice and the butter did not separate easily and so I had to soften the butter to get the ice out. My concern is/was that the soapy water had mixed with the butter enough so that if I tried to defrost it it would defrost into a sludge which is butter being broken down. My fears were confirmed. After sitting in the fridge, not the freezer, for about a day the ice is melting and the butter is not separating, rather melting down into the sludge.

I have about of month's worth of what I consider medicine in here and I will eat soapy butter chunks if I have to but I'm just wondering if there is some type of secondary wash I can do to get the cannabinoids (or most of them) from the soap/butter/water solution. I was thinking about rubbing alcohol but I'm not sure how that would work or even if it would.

Any thoughts?

 

[skillet]

Well that sucks, there can't be that much soap in there though can there? I'd probably take a small amount of the butter/water to experiment, try adding lots of warm water to it, stir well or shake it and see if it dilutes the soap enough to help the butter separate. If that works then you can wash it again with more warm, fresh water, and hopefully get most of the soap out.

 

[A Lucid Pet]

there can't be that much soap in there though can there?

That's what I was thinking! Palmolive concentrated dish soap is pretty good I guess lol.

I'd probably take a small amount of the butter/water to experiment...

Thanks! That's a good idea. I'll give it a go.

 

[skillet]

So... what happened?

I'm gonna repeat my earlier question, does anyone have a summary of selectivity for different brain areas of various antipsychotics? Pulling all the info together is going to be a giant pain in the ass, and if someone has already done it...

 

[Vader]

Could GHB form a polymer?

 

[Iodjini_dk]

Yes, but the polymerization works quite poor without a catalyst. I would say under normal conditions it is highly unlikely that GHB will form a polymer.

 

[Vader]

Thanks for the answer. As a follow up, would such a polymer be a substrate for esterases and so be an active prodrug in the same way as GBL is?

 

[sekio]

I think since the polymer unit is small enough it would hydrolize in acid, so I see no reason an enzyme wouldn't speed the process.

 

[Iodjini_dk]

This paper: http://www.sciencedirect.com/science/article/pii/S0142961204009068
Has some info on it. It seems that the polymer hydrolyses into GHB in vivo, but I cant quite figure out if it is fast enough to work as an actual prodrug for GHB. I would imagine the polymer has to hydrolyse fast enough to reach an appreciable plasma concentration of GHB.

 

[Vader]

How do forensic chemists differentiate heroin from different sources? In particular, how do they differentiate SEA and SA heroin? I understand that the answer to my question might involve synthesis discussion, if so please ignore me.

 

[Iodjini_dk]

Its close to impossible to remove impurities from the synthesis completely. The character and amount of these impurities depends on many things like reagents, purity of reagents, concentration, temperature, reaction time, method of purification, storage and so forth. You can say that every batch of drugs has its own fingerprint (given that one has the means of analyzing it). This is how forensics can keep track of different batches which can help them trace it back to the source and furthermore ban new precursors.

Its also a great field of interest for pharmaceutical companies as they can investigate the synthesis methods of other companies by analyzing their products. Even pharmaceuticals of very high purity contains trace amounts of synthesis bypr

 

[Munroe]

from what i've read 5-methyl-mda proved to be inactive.
I've read reports of 2-FA, whats the reason nobody has considered 2-fluro-mda or something similar?
Inactive, instable or too expensive to make?

Or does the same rationale not follow that though fluorination on the 2 position on amphetamine doesn't completely destroy activity wheras it may do on mda?

 

[sekio]

@Vader: I think it's from alkaloid profiling, different poppy crops have different ratios of alkaloids in them.


I think nobody's made 2-F-MDA because 2-fluorosafrole is hard to come by.

 

[Hyperthesis]

@Vader: Iodjini_dk and sekio are both right with their answers. To determine the global origin of a heroin sample the following methods are used:

a) Profiling of accompanying alkaloids (as suggested by Sekio), because these very between different strains and not all cultivating countries use the same cultivar. Due to the very long history of traditional poppy-cultivation, the more recent breeding attempts, which aimed at producing poppy variations with preferentially only or few enriched alkaloids, and finally the cultivation of the plant for decorational purposes does the number of poppy-cultivars/-races goes into the hundreds (at least). Obviously, this method is only useful if you know which variation is currently grown in a certain area. This is usually investigated by police raids, taking field samples and checking either the alkaloid spectrum (eg. with GC-MS) or the genotype (more expensive).

b) Profiling of impurities coming from the synthesis (as Iodjini_dk suggested). In the particular case of heroin, this is a bit tricky, because its preparation consists apart from the isolation procedure usually only a single synthesis step. This single step can furthermore be accomplished with a very small range of avaible reagents. I don't think that I spill the beans when naming the most obvious choices: Acetic anhydride and acetyl chloride. For impurity profiling, forensic scientists usually rely on the analysis of residual traces of solvents, auxiliary bases and acids (used for the conversion of the freebase form into salts and vice versa).
In some regions (eg. NZ) certain methods for heroin preparation emerged that facilitate analysis due to their somewhat 'exotic' character. A keyword in this respect is the so-called 'homebake'-method.

c) Profiling of adulterants. The source of a drug is not necessarily limited to its place of cultivation (from the governmental point of view), but also includes trafficking routes. Because adulterants are usually not added at the first level of the production-distribution-chain, adulterant-profiling can help to identify shipping routes or the participation of a certain drug cartel. As a related example, think of the recent rise of levamisole as cutting agent in coke. Adulterant-profiling also helps to distinguish between home-made vs. clandestine-made (ie. large scale) heroin, because for the former readily manufactured preparations are frequently used (pills!). These contain either very specific adulterants (sometimes so specific that one can even name the specific brand, which was employed) or, which is quite suspicious on its own, next to no impurities at all (indicating pharmaceutically pure morphine as source).

Further details are kindly provided by the United Nations: http://www.unodc.org/pdf/publications/report_st-nar-35.pdf

 

[Vader]

Thanks for the answers guys!

 

[television82]

What's the chemistry behind benzo withdrawal, and why is their no cross tolerance with the GABAb agonist Phenibut?

 

[alkap555]

Question A--Chemistry behind benzo withdrawal:

As you prob know, Benzos primarily act as allosteric agonists of the benzodiazepine-GABA(A) receptor complex. Agonizing this receptor effectively increases the net amount of inhibition that occurs upon binding of GABA to it's specific site on the BZD-GABA(A) receptor via increased frequency of chloride ion channel opening. This allows for increased Cl- ion influx into the postsynaptic neuron (mechanism of GABA-inhibition is actually reversed for presynaptic inhibition), which hyperpolarizes the postsynaptic neuron making it more resistant to subsequent depolarizations (makes it more harder to "stimulate" or "fire" which occurs via depolarization.

Chronic use of benzos lead to downregulation of the BZD-GABA(A) receptor complex via multiple homestatic mechanisms including short- and long-term adaptations likely involving (at first) BZD-GABA(A) receptor internalization (endocytosis). Other long term mechanisms (that I do no know off top of my head) for receptor downregulation are probably involved, but the net effect is the same: reduced BZD-GABA(A) receptor density. Upregulation in opposing neural circuity/neurotransmitters (glutamate etc.) also likely occurs.

When benzos are stopped, the decreased (downregulated) BZD-GABA receptors and GABA neurotransmission in general lead to unopposed excitatory neurotransmission. Subjectively, this is the "benzo withdrawal," and as expected is largely characterized by "opposite effects" of benzos: anxiety, insomnia and many more shitty things.

This withdrawal persists until the homeostatic mechanisms of the CNS re-adjust (upregulate) BZD-GABA(A) receptors and GABA neurotransmission to their original levels. Before this re-equilibration occurs, however, there is a net excess of excitatory neurotransmission which is responsible for the hell of withdrawal.


Question B--lack of phenibut cross tolerance:

Benzos only bind to a specific subset of GABA receptors known as the GABA(A) receptor (and still only binds a smaller portion of these...the "BZD-GABA(A) receptor complex). Phenibut, is a GABA(B) agonist and has no affinity for the GABA(A) receptors involved in benzo pharmacology. GABA(B) receptors are inherently different, being G-protein coupled receptors rather than Cl- ion channels like GABA(A), and are largely distributed in the peripheral nervous system (more so than GABA(A)) and spinal cord.

So the two drugs are not cross-tolerant b/c they bind two distinct receptor subtypes... That being said, stimulation of either GABA(A) or (B) has a similar effect of net inhibition and they may be of some use interchangebly in terms of managing withdrawal symptoms. For example, GHB withdrawal (a putative GABA(B) agonist) can be managed with high-dose benzos (GABA(A)), although the gold standard is baclofen (a Rx only GABA(B) agonist)

Sorry if this is not detailed enough or overly detailed....not sure what sort of answer you are looking for. Hope that helps.
Sources: Graduate degree training in neuropharmacology and neuroscience