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

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What's the story with nasal/sublingual administration of water insoluble drugs? I often see people on here say "that's not soluble in water, you can't snort it", but people seem to have success taking benzos sublingually, and snorting freebase DMT. With the DMT, if it's active they can't just be swallowing it, so what gives?

You can snort drugs that are not very soluble in water, like triazolam, or DMT as you said.

When people say "that's not water soluble - you can't snort it" they really don't know what they are talking about.
 
Do I understand correctly that the 3-meo-pcp it is a ether of pcp?
One guy told me that only alcohols can form esters (I don't quite understand what does it mean)
 
3-MeO-PCP is an ether-derivative of PCP, that's correct. Please note that this is merely a formal way of naming it and doesn't have anything to do with the synthesis of 3-MeO-PCP. It is (partially) correct that only alcohols can form ethers (...which PCP is not!). Only partially, because you always need an alkylating agent (like a halogenalkan a lá methyliodide), which is not an alcohol itself. Anyway, then again isn't 3-MeO-PCP made from plain PCP.

The term "to form an ester" means by the way that a molecule with an alcohol-function, ie. a OH-group can be derivatized into an ether, ie. O-alkyl-moiety, with an appropriate reagent. For the latter exist numerous possibilities, but synthesis-talk is forbidden here, hence no further details from me.
 
I'm trying to do my own research but I can't find anything. What compounds are analogues of sugars?
Sugars per se can indeed be turned into a drug, the most famous transformation being the fermentation of glucose into ethanol by yeast. Apart from this example it gets hard without unnecessarily much effort.
The point is that with enough patience, material and money (!) one can turn eg. glucose in almost anything that you want, but this would include several rather pointless chemical transformations and is hardly a viable approach. In other words: It's chemically possible, but absolute retarded, because a much too expensive way.

Apart from that I can imagine a prodrug containing a sugar moiety, which gets cleaved off in vivo. That wouldn't render the sugar psychoactive on its own, but at least it would create a molecule containing a sugar-residue with psychoactive properties (...after one or two metabolisation steps). Not exactly what you asked for, but somehow related.

Analogues of sugars (in the narrower sense "carbohydrates", or in other words molecules fulfilling the general formula CxHyOx; x = 1 & y = 2 for glucose, 2 and 4 for sucrose respectively, etc.) are:
- sugar-alcohols, like mannose
- sugar-acids, ie. aldonic acids, ulosonic acids, uronic acids, aldaric acids (see Wiki for details)
- sugar-amines, like glucosamine​
...and others.

None of them is psychoactive on its own, but some act as drugs, for example as laxative (eg. mannose).
 
Can you convert a sugar molecule into a drug?

I was a bit enamored of pharmaceutical carbohydrates a year ago, because their structures are quite beautiful. Here are examples:


Topiramate is directly synthesized from fructose (google the synthesis map):

191px-Topiramate.svg.png
from
Beta-D-Glucopyranose.jpg



Fondaparinux (an anticoagulant):

800px-Fondaparinux.svg.png



And of course heparin:

591px-Heparin-2D-skeletal.png
 
Ah see, I didn't ponder enough :) All three abovementioned examples are indeed established drugs, although hardly psychoactive ones.

Good point. The anticoagulants don't even target any receptors/tissue.

Topiramate is psychoactive. On a related note, even glucose is psychoactive (this is why epinephrine has a fleeting stimulatory effect).
 
Calling glucose psychoactive on its own would stretch the term "psychoactive" immensely, if you ask me. To what kind of activity in particular are you referring to?
 
Calling glucose psychoactive on its own would stretch the term "psychoactive" immensely, if you ask me. To what kind of activity in particular are you referring to?

Actually Hyperthesis I'd really appreciate your informed feedback on this. A shot of from an Epi Pen has a transient stimulatory effect. This is because epinephrine converts glycogen stores to glucose, thus increasing the rate of systemic and cerebral metabolism by elevating plasma glucose. The reason this is interesting to me is that the cultural notion of an "adrenaline rush" is not all semantics and has actual biochemical underpinnings.

In simpler words, good feelings and euthymia (or a contented, upbeat mood) are always attainable, even without medication. Is this a function of blood glucose?
 
Uhhhh, difficult, but nonetheless fascinating question.

First, I would not call increased glucose-levels resp. metabolic rates a psychoactive (re)action per se. I acknowledge that there are of course certain psychological effects felt, but I think that these are within the natural limits of what we just feel when blood pressure, heart rate etc. go up or down.
The stimulant effects from an epinephrine-pen shot derive IMO from epinephrine's own psychoactive action, respectively from its action on the heart and cardiovascular system. The time it takes to trigger glucose-release from glycogen-storages is certainly enough to get the drug into your brain as well.

In simpler words, good feelings and euthymia (or a contented, upbeat mood) are always attainable, even without medication. Is this a function of blood glucose?
If you have ever seen a patient with diabetes mellitus being heavily hypoglycemic than you know that blood glucose levels definitely influence the mood!
 
Is there any threshold human dose at which dextroamphetamine/methamphetamine neurotoxicity manifests itself? For example, significant at 20 mg but transient at 5 mg?
 
No. The range can't be defined precisely due to individual differences. This is just wishful thinking...

Any estimates? How are we supposed to make informed decisions without any reliable data to guide us then? It seems we just have 50 articles that say different things.
 
When examining the activity of monoamine releasers, we examine efficacy rather than binding affinity, as most of their activity is from reverse transport rather than prohibition of reuptake. However, does efficacy in vast excess of what we'd otherwise expect (that is, as we'd expect from a mere reuptake inhibitor with the same binding affinity) directly imply activity as a releaser? Or would we need additional confirmation, independently demonstrating affinity for transporters as substrates?

ebola
 
In rats it doesn't take much, I think 1mg/kg

http://www.ncbi.nlm.nih.gov/pubmed/12452543

I think bottom line is not to do meth if you don't want neurotoxicity. Amphetamine is a reasonably safe alternative in that regard.

It would be great if there was a section on neurotoxicity in the Bluelight Neuropharmacology Text, discussing the relative neurotoxicity of methamphetamine, amphetamine, MDMA, Methylphenidate, Cocaine, and other recreational/psychiatric drugs besides stimulants.

This is against intuition so to speak, but it's interesting "Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701286/
 
It's not that counter-intuitive: methylphenidate appears neuroprotective insofar as it limits methamphetamine's efficacy (and indeed, they examined proposed mechanisms at DAT and VMAT2). Less intuitive, however, are the proposed effects on genetic expression related to vesicular formation. It's here that I think my knowledge incomplete.

ebola
 
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