Clubcard-can you personally vouch for observation of the aqueous demethylation of DHC to dihydromorphine? if so, it would be interesting, since I've sampled the 6-AcO-monoester, but never dihydromorphine itself. And damned if I could bring myself to cleave the ester of such a tasty, prime opioidergic specimen. The use of the anhydrous acid and GAA can facilitate the esterification as well as dealkylation.
One thing I've been longing to put to the test, is substitution of glacial propionic acid for GAA, same theme, anhydrous HBr in glacial propionic acid. Mainly because I've already sampled a series of ester derivatives of morphine, of lesser known use, the benzoyl ester, the n-butyroyl ester (ick...that one will be fun for people unused to confining horrid fumes. The acid anhydride is a truly filthy little monster, that if chemistry were to possess a gestalt sentience as a field, and creativity of it's own, would just have to be a sickly lurid green colour, the sort of hue that would conjure in the minds eye of men, the shades of vomited, congealing bile, perhaps t(a)inted with a fair bit of the color of earwax, and a habit of slowly burping up slow, languid bubbles of corpse-gas, slithering down the sides of an opened bottle like the putrescence from a bursting corpse, and the sickly, corrosive clouds that would have been known to the unfortunate military victims of chlorine gas attacks in the era of trench warfare, slowly oozing it's corrupted way forward with gibbering, foetid glee
), obviously, have sampled plenty of the diacetyl ester way too many folk know and love, although I've never been nearly as enamoured of H as I am towards morphine itself, for whatever reasons, it has it's good points and it's let downs, but IMO the cons outweigh the pros, not really counting as much of an improvement to my taste in opioids. The n-butryic diester of morphine again, it seemed quite plain, the duration dropping immediately back down with the extension of the ester chain from C3 to C4, along with the stupendous rush of the C3 diester and potency again backed down.
C3 seems to offer a unique sweet spot as far as acyl esters are concerned, of morphine, the dipropionate ester really jumps in term of IV rush, even more so than morphine, much more than heroin (street or otherwise), the duration also anomalously spikes to easily two or three times that of diamorphine or morphine, of course, excellent analgesic for those actually in pain (my joints hate me, I hate them right back, along with the trochanteric bursitis in both hips that my altered walking gait has brought on and the nerve damage inflicted by the surgeon's blade whilst intending to fix the knee, and remove some splintered bone fragments that had been until then, free to do as they saw fit, to float about and get stabby, along with causing my knee to lock, or to collapse suddenly with no predictable pattern or warning. Some also irritating the patellar tendon, causing tendinitis, and generally making quite a bastard of themselves), I'm on morphine as main rx'd pain med, meant to be oral, but given insufficient to use it thus after switching to morphine from XR OC80s twice daily, and now using a combination of IM morphine and lower-dose IR oxycodone, the latter scripted at 80mg/d in the form of 10mg capsules for breakthrough and fine tuning of the day as requirements present themselves; but it was a mixed blessing, I converted to the more desirable morphine, but just my luck to have to explain the very concept of differences in routes of administration affecting the bioavailability of a drug, and even BA itself. So they pretty much assumed and left me with what would just about work, when injected, assuming it would also do the same thing when swallowed as an XR formulation.
Way, the, fuck, to, go; doctor. And to persistently ignore it being pointed out and explained in the most simplistic, yet accurate terms that the individual told me he could understand when explained to him, that no, an oral dose of morphine ends up with about 75% of it being chewed up in the liver and spat out screaming, with the remainder acting. And that weight potency itself is less, significantly,than oxycodone. Did they make the adjustments necessary?
No, did they fuck. Just got more suspicious and judgemental for the part of most of the GPs at the surgery, never mind that a simple and polite explanation of the biology of morphine metabolism and that of oxycodone, per os, was provided and the disparity pointed out.
Only ended up with what is now a just about sustainable total dose of pain medication with the oxy put together with the morphine, the latter having to be delivered by the spike, back-stabbing double edged sword that it is so (in)famous for being to the soul of a man who will pick up the point, and for a fair while, it wasn't sustainable, and modifications HAD to be assayed and the cream of the crop sown and reaped, for both quality and quantity, it turned out to be the dipropionyl ester, with it's anomalous peaking in multiple modalities, E.g weight potency compared to C1 shortening or C1 incremental lengthening with a straight chain acyl ester, the n-butyroyl diester, both dropped precipitously off in every respect, with DPM taking up a sweet spot perhaps akin in opioid chemistry to the island of stability for transactinide isotopes, in the realm of nuclear physics.)
Nothing terrible about di-n-butyroylmorphine compared to diacetylmorphine, pretty similarly bland, cannon fodder opioid material basically, increased potency vs unsubstituted morphine itself as expected, bit nothing like that sharp spike at C3-disubstitution. I have not yet tried the obvious interesting experiment of instead of n-butyric ester, using isobutyric diester, as a probe to try and determine whether a branched chain has any influence on the potency, etc.
It'll have to bee done when time and resources permit, of course, on a test scale of a few doses, IV, SC, and IM.
Still, of any morphine derivative that has ever come under my inspection, dipropionylmorphine is the outstander, outlier, bastion of unusual characteristics compared to it's immediate neighbors, with only alpha-chloromorphide proving to be deserving as yet of such a thorough evaluation, although in the latter case, that was precisely because it behaved so utterly unlike a MOR agonist at all in-vivo, with the weird purely cerebral psychostimulant effects without peripheral stimulation, as well as, in MOR agonist WD, a mild attenuation on it's own but nowhere near cessation of the unpleasantries of opiate withdrawal. But seeming modulatory effects if another, weak opioid, such as a CWE of DHC or codeine were used, or codeine syrup as an emergency, potentiating, but without the MOR agonist, just this weird cerebral...speeding up of thought processes, not excessively racing as with too much amphetamine or the like, no cardio push noted, but side effects did indeed prove to be the factor which limited the dosage, although the weight used at maximal dose, I no longer have the notes from, after a HD failure.
But the limiting factor on escalation of alpha-chloromorphide dosage, proved to be clonus in the distal extremities, myoclonic type twitches of the hands, froarms, as well as lower legs and ankles especially. Since I have seizures, some of them being of the atonic type, but the others, are myoclonic, or one moving into the other, typically myoclonic for a shortish duration before paralysis ensues, with some conscious awareness of the environment, although sensory perception is extremely skewed and warped during a seizure of the atonic type for me.
So, I've become both vigilant for the signs of either type about to slip the leash and go raise Cain, and, at least able to note down prognostic signs before a full blown attack that needs immediate termination with chlormethiazole, often with the help of my old man to physically put a few capsules in my mouth, if I've either gone fully atonic, or in the myoclonic phase or isolated type and twitching too badly, too often to have any hope of reaching out for the bottle I always keep close at hand, much less opening the child-proof cap, taking 2-4 capsules out and getting them from hand to mouth instead of throwing them at something or someone or dropping them, and of course, being unable to close the bottle myself.
And the top tier dosage of the alpha-chloromorphide, prepared via SOCl2 chlorination of morphine sulfate, by slow dropwise addition of a solution of thionyl chloride in ice-cold anhydrous acetone, made immediately prior to use, into a well-stirred similarly cooled flask containing the morphine sulfate in the same media, followed by a methanol quench of SOCl2 surplus to requirements if any there bee, vac distillation off of solvents, recrystallization, ensuring the PH balance was right, adjusting with dilute HCl and dilute sodium bicarbonate if needed, it definitely felt as if, were I to have pushed the dose any higher, it would have triggered a seizure, and of that, I have as little doubt, as I have that a chunk of sodium metal, thrown into water, ends up giving off copious hydrogen gas, ending up ultimately as NaOH, with plenty of skittering about the surface of the water and repeated explosions and pops bathed in the yellowy-orange of the sodium D-line when the flames begin.
I have to wonder, given the nature of the beastie, if it might be a DOR agonist ligand, since some, but not all of the delta OR agonists show convulsant side effects in excessive dosage, whilst profoundly potentiating the action of MOR agonist analgesia. The other candidate mode of action would be that of an antagonist at strychnine-sensitive glycine receptors, the potential pharmacophore for such ligands lurking, as it does within certain of the morphinans spawned from our sweet, langourous Papaver friend, in the guise of thebaine. And possibly oripavine.
Strychnine has, to my understanding, and reading of certain books in my scientific library which go back to the late 17th century AD, been used in controlled, very small quantities as a psychic energizer and stimulant. Although of course, the consequences of an overdose would be of the direst and most awful nature, and being I'm already taking antiseizure medication (the chlormethiazole, both as prophylactic and active response med), I don't particularly harbour any great enthusiasm or desire to procure any strychnine to compare alpha-chloromorphide to low doses. A guy with known seizure issues willfully consuming an infamous convulsant poison doesn't strike me as the best thought out plan in the universe.
I have no ambitions to bend my spine over backwards far enough to suck my own dick, donald 'narcissistic ambulant scrotal teratoma autofallatio dilletante' trump style.
Really, that isn't a look that would look good on me, foaming at the mouth, eyeballs rolling into the back of my skull as I stuff my head up my own rectal sphincter, bent backwards until my spine breaks, assuming I don't first choke on my own colon, definitely not stylish, attractive, or befitting a man of the autie species.
I'm all for exploring unusual drugs, but bioassaying outright poisons isn't an area of my admittedly deep interest in toxicology I have. If poisoned somehow accidentally, or by an animal, then for sure, I will eagerly (whilst being treated in as quick and appropriate a manner as possible of course) take note of things such as the time course, the subjective sensations, the external effects, any aftereffects, since if I am going to be miserable and feeling sorry for myself after, fr.ex being given a nip by a momma Latroectus spider who'd just given birth to two egg sacks, and was for once, far from her typical placid 'run and hide and try to pretend I'm not here if I can't see you, you can't see me either' approach to vibration, such as that of fingers delivering post-laying cricket snacks to my wee lady's very maternity bedside, and going for me defensively, to somewhat of my shock, knowing just HOW non-confrontational Latros are as a family, even that, accidentally provoked bite, my fault of course, not her's, surprised me a lot even after laying her egg sacs, when feeding my sadly, and truly abhorrent way of being murdered to a spiderling, death of my girl and her young, after the pigfilth raided my place on a blatantly trumped up, false premises warrant just to gain entry and inflict what damage to lab equipment they could to spite me, and that time even MICROWAVING my wee girl and her children, both the mother brown widow and all her babies in the one egg sack which had had time to hatch, and the other one destroyed the same way, as yet unborn.
Butchered, MURDERED in cold blood and hatred of that which does not appear to conform to typical society, law breakrer or not, and certainly despising an autie who just has too much of a far, FAR too deeply-rooted and inherent bent towards the siren song of the scientific arts to even contemplate allowing such bullies and thugs to deprive him of the lab he loves so much, his life's work and personal, utterly private sanctum sanctorum, Even it's twice being utterly destroyed, that just raised his blood to boiling point and hardened his resolve, dedication and determination that it must rise once more phoenix-like from the ashes of it's own death, to rise, in greater glory and sophistication than ever the previous incarnations were, in either of the twofold cases of total destruction, blatantly illegally, being charged with no crime whatsoever. The filth ought to know better than to try and take from a Kanner's autie, his personal most treasured creation and possessions in all the world, that are fuelled by speshul interest-backed devotion and dedication, and a true labor of love. Break even a single piece of glass out of malice, on the part of some porcine excrement made flesh, and his own rule is to of course buy a replacement piece of the kit , but to buy another two, and hell, every malign blow ever struck against my precious, priceless personal temple-shrine to his inner spazz, free to feel even more at home, just sitting there to read journal articles and books, as a general polymath, but one with a particular predilection for nothing less than the sheer innate biological all-consuming desire to personally claw every fragment of knowledge and discovery from the most basic way to cook a bowl of porridge and flavour it to personal perfection, to literally, byte by byte, personally encoding each and every single possible bit, byte, Qubit, spin- or/and valleytronic possible piece of information-devouring processes and the information in existence, as if addicted to mainlining technology-knowledge as if shooting up the distilled and salted essence of knowledge and technology itself, every single possible thing to be known in the physical universe, and any other universe that might form a greater multiverse, although at the same time that ABSOLUTE possession of every single piece of knowable data in any form of existence ever, would be a nightmare worse than death, for it would mean the prolonged life span through technological means for a long long time, and at the same time, if actually knowing EVERYTHING, it would bear with it, IMO, the curse of knowing that, and knowing that there is thus, not a single drop more knowledge that is there to be learned and known fix of discovery, creativity and research bearing fruit of further knowledge cannot bee, for all, a factual singularity, in effect, would take root, and there would never again, in a long eternity, be a single discovery left to make.
To know all, and to know one knows all...that, whilst at once, that to be strived for, is only so in the knowledge that it would be impractical to accomplish the goal. For having done so, the journey must perforce end, and the knowledge-junkie autie that I am, would know there'd never be another fix in existence, and a fate worse than death, indeed, a kind of living, soul-destroying death, in the absolute and secure total comprehension that another jolt and euphoric fix of a discovery anew, or creative process spawned by oneself had been made that can be made, and that which at the base level, codifies my very being, has been reduced to a state never to know such bone-deep ecstatic delight again, upon harvesting another juicy piece of knowledge.
*shudders*....the path, would essentially end in a singularity. The journey at a forced end, never to feel the sweet, delicious rush of learning a thing ever again in what would undoubtedly be a massively prolonged lifespan due to technological innovations. Its an odd thought, to know that it is a mercy that one cannot accomplish that which life itself drives them to seek. The journey being just as innately, fundamentally vital as the discoveries themselves, and that marrow-deep insatiable HUNGERING, to be sated without possibility ever to know again the psychological lust for imperative continual knowledge-acquisition....that is a grim thought that has, literally, given me some of my most chilling nightmares, in the past.