goodvibesandchemnotes

[goodvibesandchemnotes]

tl;dr: math IS an art + fuck education

response to https://youtu.be/o1eLKODSCqw

also, the end of this video poses an open question that I'd like to close directly: math IS art. popular opinion says it's all rigor… so is grammar or playing any instrument or performing any artistic craft. is your favorite book just word after word after word that you have to memorize definitions of? no, it's a story told with those words, you just have to learn all the letters and then all the vocabulary and then all the grammar and…. sounds like an awful lot of rigor, no? math is about numbers and equations about as much as music is about finger placement (i can hear the violin teacher snapping at me already…) or literature is about letters and words and rules of grammar. NO! IT'S AN ARTFORM! it's what you CREATE with those tools of rigor! And you can break the rules once you're experienced enough, like the invention of calculus, or Chaucer/Shakespeare merging languages to invent a new one and sometimes inventing BRAND new words to describe concepts they needed to express… and the cherry on top is that there's no end goal of mathematics. All the sciences have a goal, to answer specific predetermined questions until a topic is resolved and the next confusion can be addressed, while mathematics sits with music and painting and handcraft in that there is no true end goal but to illustrate patterns. Sure, it has its practicality, but so did clay pottery, and bronzecraft, and ironcraft, and writing, and optical glass, and…. the list goes on. Mathematics is an art, the rigor is just of a different variety than many other artforms.

[goodvibesandchemnotes]

My two favorite orgo reactions!

FISCHER RXN

The Fischer esterification is a reaction as essential to the beginner organic chemistry student as it is to the layman observing his fruit ripen. Esters are a weakly polar, organic compound of chemical characterized by the dehydration of an acid (generally carboxylic) and an alcohol; as such, they are named X-yl Y-oate for the alcohol X-ol and the acid Y-oic acid. As characterized by the carbonyl and the carbon-oxygen sigma bond, the compound is in between the polarity of a comparably sized ketone above (such as ethyl acetate and acetone) and ether below (such as ethyl acetate and diethyl ether), making them miscible with each but sparingly soluble in a highly polar compound such as water or glycerol [# pubchem etoac].

Esters are highly significant in the natural world and are even known among chemistry laymen, such as wine enthusiasts, for their generally pleasant odor reminiscent of fruit (aliphatic esters) or mint (aromatic esters). This stands in stark contrast to the acrid smell and taste of most carboxylic acids and alcohols. For example, butyric acid, a carboxylic acid, is named for being the primary component of rancid butter. This response is for a good reason, when bacteria grow in over-ripe fruit, they hydrolyze the esters into their constituents (enzymatically or with increasing acidity). Over many generations, animals evolved to detect the constituents with an unpleasant smell and/or taste and associate them with rotten fruit and therefore illness.

With a clever knowledge of chemistry, this natural process of hydrolysis can be directly reversed. An extreme pH is generally required to catalyze the hydrolysis of an ester, and the reaction equilibrium in nature is driven by an excess of water. Therefore, by le Chatelier’s principle an absence of water and an excess of alcohol or acid should drive the equilibrium in the opposite direction. Indeed this is the case: Fischer and Speier noted in 1895 that in dehydrating conditions (especially over 100 C) methanol or ethanol condensed with organic acids in the presence of mineral acids [#german source]. The ester can then be readily extracted from the reaction bath of alcohol and water with a weakly polar organic solvent like diethyl ether.

In this particular experiment, benzoic acid will be esterified with excess methanol under sulfuric acid catalysis to form methyl benzoate, a compound similar to the natural product wintergreen (methyl salicylate, or methyl (o-OH)benzoate. One should note that as well as aliphatic polar solvents (most commonly ethyl acetate is used as a non-toxic alternative to diethyl ether or acetone), esters are useful as protected precursors to other compounds. For example, the Grignard reagent RMgX is an extremely strong base and would deprotonate a carboxylic acid R'COOH rather than react with the carbonyl to form a carbon-carbon bond (as Grignard reagents are intended for); however, the ester R’COOR” reacts in the way one would otherwise expect of a carboxylic acid in forming carbon-carbon bonds with a Grignard reagent.

https://pubchem.ncbi.nlm.nih.gov/compound/ethyl-acetate#section=Solubility

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cber.189502803176

GRIGNARD RXN

While the basics of organic chemistry had been known since the 1800s, and inorganic chemistry for much longer, the bridge between the two (rather directly named “organometallics”) was not understood until much more recently. The Grignard reaction is one of the first such organometallic reactions; Victor Grignard was the first to publish on the chemistry of alkylmagnesium halides RMgX (named Grignard reagents) in 1900 and was awarded a Nobel prize for this groundbreaking discovery in 1912. This discovery was so revolutionary that the field of organometallic chemistry was not even approached again until the 1930s, when organolithium reagents RLi were developed as a less sterically hindered alternative to Grignard reagents. The phenomenon of bridging two seemingly unrelated fields is significant on its own, but the discovery of Grignard reagents opened the door to modern chemistry by providing a simple and reliable way of forming carbon-carbon sigma bonds.

Carbon is a relatively neutral element with regard to electronegativity, and as such it does not readily react with other carbon atoms in molecules and preferentially reacts with more electronegative compounds. In the case of Grignard reagents, the imbalance is in the opposite direction, disrupting an already polarized carbon-halogen bond with the highly electropositive and reducing magnesium metal (via a radical intermediate). This C-Mg bond is extremely unstable (so much so that the Grignard reagent is almost exclusively generated in situ), with a strong ionic character almost resembling a persistent carbanion coordinated to an oxidized Mg2+ ion. A carbanion is extremely nucleophilic and will readily attack any electrophile (such as a carbonyl) by donating its lone pair to form a sigma bond. In the case of a carbonyl a prized carbon-carbon bond is formed, transferring the spectator MgX+ ion from the carbanion to the newly formed alkoxide ion. However, carbanions are also extremely strong bases (arguably stronger than they are nucleophiles), and any protic solvent such as water or an alcohol will act as an acid and donate a proton to form the corresponding alkane and a magnesium-solvent salt. Therefore, it is prerequisite in any Grignard reaction to keep the reaction completely dry of moisture and any protic solvent.

The Grignard reagent was first explored with carbonyl chemistry, and when named without clarification the “Grignard reaction” implies reaction of an alkyl- or aryl-magnesium halide (generally chloride or bromide) with a carbonyl of some sort. The traditional introductory example is the reaction of a Grignard reagent with a ketone to form a tertiary alcohol, where the addition is relatively straightforward and the resulting alkoxide is neutralized with acidic aqueous workup (generally with a HCl, leaving a byproduct of MgCl2 or the mixed MgClBr). The reaction with aldehydes follows similarly, forming a secondary alcohol instead, and the Grignard reagent will react with electrophiles including nitriles, alkenes, and epoxides, and (more unusually) esters.

The reaction of Grignard reagents with esters behaves most regularly in at least a 2:1 excess to the ester, where the carboxylate group is turned into a tertiary alcohol. The first equivalent of carbanion attacks the ester carbonyl to form a hemiketal, which is unstable with respect to the alkoxide leaving group from the ester and forms a ketone between the (formerly) carboxyl and the carbanion. By preserving the carbonyl from the ester carboxyl group, the intermediate molecule is open to a second attack by the carbanion to form a tertiary alcohol as described previously. However, when only one equivalent of Grignard reagent is available, the reaction will not proceed uniformly and a mix of the ester, tertiary alcohol, and intermediate ketone will be present in the product. In this experiment, phenylmagnesium bromide (itself formed from phenyl bromide and magnesium metal in situ) is reacted with methyl benzoate to form triphenylmethanol, via the intermediate benzophenone.

#chemistry #biochemistry #organic chemistry #studyblr #study blog #science #grignard #fischer #ester #perfume

[goodvibesandchemnotes]

[goodvibesandchemnotes]

You remember how a while ago rich people started paying huge amounts of money to drink dirty water? They're at it again. They're eating dirt now. Black Oxygen Organics, among others. It's fucking bog mud and compost in fancy supplement guise

What

(googles)

https://blackoxygenorganics.com/

oh my sweet lord fucking…….

[goodvibesandchemnotes]

long haul covid is now largely being called PACS. post acute covid-19 syndrome.

[goodvibesandchemnotes]

honestly even the highest concept sci-fi seems tame once you learn BioSteel™ Goats exist irl

[goodvibesandchemnotes]

lichens are so funny. like microscopic spores in the air are spontaneously making organism soup on nearly any undisturbed outdoor surface on earth and we're all just like yeah thats normal, we dont know how they keep getting away with it but every living thing in this situation is definitely having a normal one

[goodvibesandchemnotes]

In response to tumblr's new premium content policy, I'd like to proudly announce all Bud content is now officially free! It was already free, but it's also free now, too. (I tried to post Bud's first time seeing snails but tumblr shat the bed on the video upload)

Science fun fact!! Tylenol is toxic to cats (as well as antibacterial soap ingredient chloroxylenol) because they lack the glucuronic acid transfer enzymes (called UGT) that humans have. Some NSAIDs may be safe in cats, but generally gabapentinoids are used to control all types of chronic pain in cats (such as arthritis, a notably NON- neurogenic pain disorder). Dogs, however, have these UGT enzymes and can be given many more human medications safely.

Every upvote is another treat I give Bud!

#satire #selling premium #tumblr premium #tumblr problems #cats of tumblr #cats #cat #caturday #so cute #biochem #biochemistry #chemistry #studyblr #learning #nerd #organic chemistry #science #chem #veterinary medicine #veterinarian #adorable pets

[goodvibesandchemnotes]

One of my favorite plant fun facts is that the Nixon administration tried to get rid of Opium poppies (which have morphine) in America by replacing them with Persian poppies, which have "inactive" thebaine instead... thebaine is a precursor to much stronger opioids than heroin. They were aware of this at the time. They still proceeded. What happened next will shock you.

https://en.m.wikipedia.org/wiki/Papaver_bracteatum for reference, the stronger semi-synthetics are called "Bentley compounds" and are actually how we discovered buprenorphine (useful in treating opioid addiction). As far as I can tell, these thebaine derivatives never saw much action on the black market by the 80s only because fentanyl took the world by storm. Fentanyl analogues are much cheaper to produce and much less long-lasting, making users desperate more quickly; it quickly became a favorite of shady drug dealers and international manufacture and shipping of the drug has even been considered non-conventional warfare. (Hastily sourced from the Wikipedia article for fentanyl, which talks about the drug first seeing action around the mid '70s and its hard to find any record of use of thebaine derivatives after the 70s. Unfortunately, I don't know the history of the opioid market in nearly enough detail to properly confirm, but if/when I write a proper blog post about this I'll follow up with sources cited)

#hard drugs #biochem #biochemistry #chemistry #studyblr #learning #nerd #organic chemistry #science #chem #phytochemistry #history #war on drugs #opiates #heroin #morphine #vicodin #prescription #oxycodone #oxycontin #opium trade #opium #poppy

[goodvibesandchemnotes]

This is a medium effort blog. It's mostly my spur of the moment infodumps ("essays courtesy of autism" I call them) with some of my prepared notes, and a sprinkle of "ooh, that's cool!" impulse reblogs. So I don't spend as much effort on content as, say, my music, but I still tell my mom and my friends excitedly every time I post lol

[goodvibesandchemnotes]

Notes on benzomorphans!

More notes! This is a class of opioid drugs that aren't (generally) addictive... but at a cost, they induce horrific hallucinations like the Salvia divinorum plant (ever wondered why burning sage cleanses demons?).

The body has three opioid/endorphin varieties, δ (DOR), μ (MOR), and κ (KOR); the MOR is responsible for all opiate (eg morphine) effects, DOR is stimulating and "distracting" from pain, and KOR reverses opiate side effects but causes severe dysphoria (opposite mood of MOR) and, at higher concentrations, psychosis. Benzomorphans tend to be KOR agonists (like Salvia) and MOR blockers (like Narcan), but can have a wide profile of effects. They tend to act on all 3 opioid receptors; monoamines (serotonin, adrenalin, dopamine); dissociative NMDA receptors; and, the poorly understood sigma receptors (which may be useful for antipsychotics, antidepressants, and nootropics!).

Most of these drugs either never left the lab or clinical trials at best. A few notable exceptions include pentazocine and phenazocine (MOR mixed, KOR agonist) were widely used in Japan as analgesics and eventually abused under the slang name "T's and Blues" in the 70s/80s, although they have a MUCH lower abuse potential than any traditional opioid. Cyclazocine was actually used for its DYSphoric, KOR properties and used to treat mania in bipolar patients without worsening psychosis; this is comparable to the traditional entheogenic use of Salvia divinorum by Mazatec shamans. Alazocine never saw medical use, but was used in vitro to label the σ receptors for the first time, and D-alazocine has a similar profile to D-methorphanol, or dextromethorphan "DXM". This provides insight into the very unexplored DXx family of dissociative drugs, which can be used (by dissociative and σ properties) as a better neuroprotective.

I'll scratch out the few notes on DXx drugs next, then one more class (competitive antagonists, not pore blockers) and I think that'll be a wrap on dissociatives! Next unit I move on to the massive variety of monoamines, which are arguably the most important system in the brain and far too much to sum in one page. (I may ramble about arylcyclohexylamines again at some point, we made a drug named Fourphit to give mice permanent PCP brain damage and it opened quite a lot of questions on natural brain regeneration)

Have a good night, everyone! Eat your veggies and get enough sleep! Love, Alex 😴

#biochem #biochemistry #chemistry #studyblr #learning #nerd #organic chemistry #science #chem #dissociative drug #drugs cw #psychedelic drugs #designer drugs #drug addiction #salvia #sage #burning sage #painkillers #pain relievers #pain relief #chronic pain #psychology #neurology

[goodvibesandchemnotes]

Tl;dr: throwing garden snail pests in an ad hoc terrarium. Doing science on said snails. Give me ideas for science experiments on snails! Also ideas for designing easy self sustaining terrarium welcome.

🐌🐌🐌🐌🐌🐌🐌🐌🐌🐌🐌🐌🐌

Okay, I got halfway through designing a snail terrarium when I realized I don't even want snails. But, they're gonna be on my plants either way, I can kill them as they appear but that just feels... nah. So I'm gonna turn a storage bin into a plant-housing snail terrarium, if it works then it'll be extremely low maintenance or entirely closed and I can just pluck em off the plants and toss em into the Box. There will be moss, clover, and whatever local plants in a mix of local dirt and potting soil. Snails (and maybe a few soil bugs/worms?) will breathe air and eat the plants, and produce CO2 and fertilizer. Plants (especially nitrogen fixing plants like clover) will turn the waste and CO2 into fresh O2 and growth! Obviously my numbers have a massive margin of error which is why i say low effort not no effort. Perfecting a sealed terrarium is a fine art, I'm just trying to save my pepper plants.

However. There's one big issue. I... don't... have any use for snails. They seem edible enough but should I *really*? They're cute but I don't especially want them as pets? And then it hit me-- I am a mad scientist! I do science! And they're far less conscious than rats and I write papers about methodically torturing rats (studying next generation analgesics).

So... what do I do with em? If I decide to kill them I'm gonna make a baking soda volcano to flood the tub with CO2 or I'll let them commit suicide via beer drowning (they like beer, but it will very quickly kill them). But that's awful bland, and this is more fun than it should be. Yall give me ideas for my mad science career, if the experiment is good enough I may be able to show it off to recruiters

#biochem #biochemistry #chemistry #studyblr #learning #nerd #organic chemistry #science #chem #phytochemistry #snails #baby snail #terrarium #ecosystem #pet snails #pest control #gardening #garden #garden pests

[goodvibesandchemnotes]

[to a fibromyalgia/ptsd patient] *hugs* I'm sorry your brain is so fried and causing you such pain. I've seen great success in myself and others periodically taking dissociative anesthetics for PTSD and treatment resistant depression, and it works wonders for my fibromyalgia (which often had me unable to eat or walk many days without being heavily extra-medicated).

Legally speaking, I have to say that ketamine is the only drug properly indicated for this purpose, and it (as well as most derivatives) is a schedule III substance that is illegal to obtain without a prescription from a doctor. It is mostly safe and effective, with the only risk being increased dissociative tendencies (this isn't even a problem for many people, it's only if your dissociation tends to flare on and off and is upsetting/disabling. For those with constant dissociative issues its been anecdotally observed that dissociative drugs can actually strengthen a patient's grasp on their dissociative issues and make them better, but remember anecdotes aren't science). It is more effective than many first and second line antidepressants in these cases!

Scientifically speaking (for educational purposes only of course!), I also can't let it go unsaid that there are several grey- or legal dissociatives that can produce a similar effect... but each has its own safety profile. DXM can be *EXTREMELY* dangerous when taken at anesthetic doses with certain antidepressants, and most ketamine derivatives are not fully studied and we don't know what interactions they could have. From our understanding, DCK and 2FDCK seem pretty safe, as well as OPCE (close relative of DCK). The MXx series tends to run similar risks to DXM albeit a much cleaner, less "drunken" experience. Tiletamine (animal replacement for ketamine) is functionally identical as far as we currently know, but is only sold as Telazol in combination with sedatives that can cause fatal respiratory depression and Telazol should never be taken by humans under any circumstances.

While dissociative drugs have addictive potential similar to alcohol, they are not strictly physically addictive drugs. Repeated use builds tolerance, and withdrawals from constant heavy (usually non functional) users have been seen, but compulsive (especially daily) use is rare and only in individuals with especially addictive personalities and/or looking for an escape from severe psychological distress. An exception is any mania-inducing drug, which causes compulsive redosing (but is still significantly less addictive than opioids or stimulants). For common reference, a rule among recreational users of DXM is "1 week per 'plat'/150mg"; you can take 150mg again next weekend and not have many tolerance issues, but wait a month after taking a 600mg (very high, fully anesthetic) dose to avoid tolerance or psychological addiction. Additionally, dissociatives present cross-tolerance, so someone who frequently abuses DXM would require a much higher dose of ketamine for the same effect as a dissociative-naïve patient.

With the 3-MeO-PCx series, there is a flood of dopamine and serotonin that can spark new brain connection and give a remarkably positive experience. BUT! These carry both the risks of DXM/MXE (vomiting, heat stroke) AND potential mania which, left uncontrolled or in susceptible individuals, can cause psychosis. There is also an issue of potential compulsive redosing on 3-MeO-PCx (NOT 3-MeO-OPCx or the MXx series), so it's recommended not to have large quantities readily available when using (which is dangerous and often illegal). The safer users tend to binge a few doses and then avoid it for weeks to months.

Whoops, wrote another essay. I'm happy to share my useful notes on treating fibro whenever they're fully compiled, I've found absurd amounts of success especially in treating my severe cognitive damage from it. Above all, be safe!

#biochem #biochemistry #chemistry #organic chemistry #science #phytochemistry #nerd #chem #learning #fibromyalgia #ptsd mention #ptsd recovery #ptsdawareness #ptsdwarrior #ptsd tw #fuck fibro #fibrolife #fibrowarrior #fibro flare #fibro tag

[goodvibesandchemnotes]

A conversation about the new arylcyclohexylamine ban in Germany:

As far as I know, there are not many possible structures left.

If you check this list: https://en.m.wikipedia.org/wiki/Category:Dissociative_drugs, most of these drugs are Arylcyclohexamines with just a few exemptions. Salvinorin analogues could be a candidate. Also maybe something related to Amantadine: https://en.m.wikipedia.org/wiki/Amantadine.

I’m no chemist and this is pure speculation. I just wouldn’t expect a quick solution as with the novel lysergamide they just released.

Au contraire!

Ephenidine is a bit too PCPish for me to recommend and methoxphenidine isn't much better, but that class is worth investigating to see if we can make a safer derivative (OPCE vs PCE alone is a world of difference, is there an equivalent -phenidine?)

Etoxadrol is a rather clean dissociative without MXE or PCP like additional effects. It's a personal fascination of mine that doesn't seem to be on the white or grey market, but proved its purpose in animal trials. There could be many flavored derivatives of this, though. And I'm excited!

Adamantane derivatives (hell, someone even postulated aryl-adamantyl-amines. I'll link their blog later) are very promising for therapeutic research, but haven't caught on recreational for a handful of reasons, side effects, duration of action, etc.

This isn't even addressing dextromorphinans like derivatives of DXM (DXA has an even stronger affinity for σ receptors, one of my all time favorite drug targets), benzomorphans like alazocine (which are a pair of κ-opioid agonist and NMDA antagonist mirror images), competitive antagonists like the phosphonate analogues (WHICH HAVENT BEEN STUDIED ENOUGH DON'T JUST FUCK AROUND WITH THOSE), and all kinds of novel drugs. Aptiganel is on my wishlist, it's not controlled or even recognized as a drug, but chemical vendors may have it. Ditolylguanidine is a simpler chemical analogue.

We have plenty of options ahead!

Diarylethylamines (like MXP, Ephenidine...) are sadly already covered under the German Phenethylamine blanket ban.

I could also see a possibility for Prodrugs of Arylcyclohexylamines (similar to 1P-LSD), but I'm not really familiar with all the enzymes that could enable this.

Ah, all things considered a ban on ephenidine isn't the worst. As far as drugs go, di&ephenidine are more trouble than they're worth, don't want some poor fucker thinking they've ordered the next MXE and fall into schizophrenic symptoms for a day and a half (ephenidine is extremely close to dizocilpine which is literally used to mimic schizophrenia). Shame the whole class is banned, though, I wonder if there's a PCE vs OPCE type distinction that can be made to improve safety profile.

Hmmmmm acetylated derivatives COULD be a thing? Not sure offhand what would affect metabolism without ruining the binding profile. For a class of drugs we've "exhaustively" explored, we know surprisingly little about what all ACHs could do. ACH as a scaffold is closer to phenylethylamines/amphetamines in variety, a massive range of mostly dissociative (rather than mostly stimulant) drugs with all kinds of binding affinities. We need the next Shulgin for horse tranquilizers.

#biochem #biochemistry #chemistry #organic chemistry #science #chem #arylcyclohexylamine #drugs cw #hard drugs #psychedelic drugs #dissociative fugue #dissoziationen #dissociation #dissociative drug #mxe ketamine #ketamine #pcp #designer drugs #pharmacology #germany #europe #research chemicals

[goodvibesandchemnotes]

I DID A THING

This is a color-coded chart about ketamine derivatives, or "arylcyclohexylamines". It doesn't entirely tell you what they DO (that's a lot of information) but it does explain how the names correlate to the shapes. This isn't perfectly organized, but aims to cover the major recreational and pharmaceutical drugs in the category.

This is a very wide category but these are mostly dissociative drugs that serve as (human and animal) anesthetics and recreational drugs, either mostly harmless "club drugs" or derivatives of the horrific PCP. What blows me away more than anything is how chemically similar these are. Without getting too technical, the red "O" takes away most of PCP's manic and psychotic properties; replacing P (piperidine, blue) with E (ethylamine) makes PCE more potent; and, now we have two steps of association between the stuff they use to anesthetize your cat and the stuff they use to induce violent schizophrenia and godlike strength. Those are two points on the spectrum, but these drugs are used for everything from treating strokes to PTSD/depression to even tinnitus!

Now, it's human nature: 1)when given something that turns your brain off, you're gonna want more of it, and 2)when told no, humans can be very crafty. And *very unethically* do in 5 years where researchers need 50. In particular, MXE was a nightclub favorite, being a serotonin-inducing relative of ketamine. Disgruntled by their lack of chemically induced warm trance-y vibes, the club scene soon included close derivatives like MXPr and MXiPr. And disgruntled by their lack of whatever the hell inspires PCP users to use PCP, the designer drugs scene soon included all sorts of derivatives.

This segues into another important detail, the number and 2-3 letter code before most of the acronyms. To all the non-chemists, this is whatever we add to the first P (phenyl), the orange hexagonal ring. Generally speaking, adding something thats more negative (HO, MeO, Cl, F) at the #2 position will make the drug act ONLY as an anesthetic, the #3 position tends to make the drug release more serotonin and subjective "warmth", and the #4 position tends to retain the manic and psychotic properties of PCP and derivatives. Adding a "Me" (methyl, -CH3) doesn't tend to make a big difference, meaning 3'-Me-PCP will act almost identical to PCP but 3'-MeO-PCP will have a drastically improved (but still insufficient) safety profile.

There's one odd child in the family, 3-HO-PCP. This one uniquely acts as a mild opioid (as well as "warm", manic, and overall dissociative anesthetic), in no small part from its resemblance to tramadol. Tramadol is a mild opioid often used to treat moderate-to-severe pain, with the similar serotonin "warmth" but absolutely no mania and only weak dissociative effects. Since PCP and 3-MeO-PCP are extremely potent anesthetics on their own, the opioid activity is sedative more than analgesic, and reduces the dangerous manic tendencies associated with many PCP derivatives. It is not known if 3-HO-PCE has opioid activity, or just behaves like it's 3-MeO cousin.

If I try and explain how drugs work in terms of receptors we'll be here all day, so I'll keep it in terms of "design" and "effect". The vast majority of these drugs are dissociative anesthetics, which SAFELY turn a chunk of the brain off and force the user into a trance-like state called a "hole". This is helpful in the case of protecting against damage from strokes and dementia (can't damage whats not currently accessible!), and provides a "reset" in the case of depression and PTSD that cues your brain to provide higher levels of activity when it wears off (as well as providing an out-of-body experience with powerful psychological implications, often compared to a near-death experience). The manic and psychotic (dopamine) properties can be suppressed by adding the red "O", a 2-keto group, which makes the drug significantly safer and more appealing for recreational and therapeutic use. Conversely, changing the phenyl P to a benzothiophenyl BT takes away all anesthetic properties and makes the drug purely a stimulant. Changing it to a thiophenyl T doesn't change end result much on its own, but tiletamine OTCE has seen increased effectiveness in veterinary medicine, and gacyclidine 2-Me-TCP is clearing clinical trials for a neuroprotective agent.

The big take-away here is that tiny changes to a chemical lead to massive changes in safety and effect. This can be used to fine-tune drugs to ideal therapeutic use, but its worth mention that we don't know about the vast majority of fine-tuned combinations yet to come. It's also worth mention that the designer drug market works 10 times faster than the world's professional research labs ever could. This means much quicker human results and descriptions, but an infinitely higher risk of death by overdose and poisoning from drugs no antidote has been developed for. A fantastic example of this danger is in the Spice/K2/synthetic cannabinoid craze of the early 2010s, where we found out making a cannabinoid stronger doesn't make it more effective, it makes it more dangerous. And for every Alexander Shulgin (the man who discovered hundreds of psychedelics and their effects on the mind and soul) there are thousands of unlucky 20s taking a pill they bought at a club.

#biochem #biochemistry #chemistry #organic chemistry #chem #science #studyblr #learning #nerd #hard drugs #drugs cw #ketamine #mxe ketamine #pcp #2fdck #clubbing #nightclub #research chemicals #dissociative episode #dissociative fugue #dissociative #anesthetic #opioids #painkillers

[goodvibesandchemnotes]

Just a helpful synthetic pathway I stumbled upon. Adipic acid AND N2O?! Fantastic, both useful for countless reasons. N2O is a great chemical in general though, oxidizing, solubility, obviously medicinal effects, etc. And now you can make your own nylon (i mean you'd have to turn it into adipoyl chloride first)!

[goodvibesandchemnotes]

(I'll return to this comment later and elaborate) crazy as it sounds, PCP. Not literally just giving them PCP but using it to study the interplay between monoamines and glutamate. NMDA antagonists are neuroprotective, dopaminergic drugs treat cognitive and executive symptoms as well as parkinsonism albeit at a steep cost. And yet, PCP is one of the most horrific, useless drugs we know of. Ketamine revolutionized anesthesia by removing the MAergic activity and providing a relatively clean NMDA-ant, and now it's being proven successful for depression; but they're designing non-psychotomimetic NMDA antagonists with similar benefit???

Not to mention the memantine-like drugs for Alzheimers, which work fantastically relative to the low side effects; different class of drugs entirely, different SHAPE, same receptor, same set of diseases.

Or let's just talk pharmacophore. The arylcyclohexylamines have been studied almost exhaustively, with varying NMDA, SER, NE, DA, σ, even opioid activity. Some like BTCP break the class' reputation and is a selective DRI. We can do plenty more studying, though, and we SHOULD until we fully understand.

And when we stretch the class a bit? Ephenidine (1-ethylamino-1,2-diphenylethane) and diphenidine (1-piperidinyl-1,2-diphenylethane) are much like PCE and PCP respectively; that is, VERY dangerous, with a confusing binding profile. And ephenidine can be cyclized to form dizocilpine/MK801, which is a "clean" analogue of PCP that near-perfectly simulates schizophrenia. Where in there are the other receptor shapes lost? This gives us insight to the nature of the odds-and-ends like PCPR2, a receptor that still baffles us today.

Makes sense that β-keto-ephenidine is ethyl"phenedrone" (phenyl equivalent to hexedrone, pentedrone, etc; extended α-carbon alkyl equivalent to cathinones or "bath salts"), a *nasty* stimulant. This gives us insight into the relationship between these systems in drug design. BUT we also understand how cognition and dopamine work together and while taking bath salts for your ADHD is a horrid idea, we know what drugs to give lab rats that maybe in 20 years will give us something new.

And then etoxadrol, a dioxolane (think propiophenone protected by a glycol) is FAR safer than ephenidine/PCE? But we don't know totally about dexoxadrol (PCP/diphenidine equivalent).

AND THATS NOT EVEN STARTING ON BENZOMORPHANS OR DEXTROMORPHINANS WHICH OPEN UP THIS WHOLE ARGUMENT AGAIN FROM SQUARE ONE they've already used DXM in one psychiatric combination for its NMDA/SSRI/σ properties (I believe with buproprion?) We have so much to answer and so much more to ask I didn't didn't mention the fact that we slap an isothiocyanate on these bad boys and THEN see how mice respond once their brain is irreversibly damaged in that way.