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6-monovaleroylmorphine

L

Limpet_Chicken

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Oct 13, 2005
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Query on activity and abuse potential:

6-valeroylmorphine. Whats known about it? any history of medical use? strength compared to other opioids of the 3,6-diacylmorphine and 6-monoacylmorphine esters? euphoric potential? speed of onset?
 
It would probably be quite active. I've never heard of it though. I'd be really careful as I wouldn't be surprised if it was several times more potent than morphine.
 
That was the hope. That and the hope it may possess some affinity for the GABAa loreclezole binding site upon hydrolysis (as a constituent of Valerian, not sure precisely which constituents target this GABAa subtype) I think I'd be alright trying reasonable doses of this, if I decide on it, as I am considerably tolerant to morphine/oxy, to the extent I'd have a job overdosing on morphine itself, due to solubility constraints. 5ml of saturated solution prepared with water as hot as is comfortable about hits the spot, so to speak. So, OD isn't going to occur too easily, although of course I am not about to get careless. I will be able to estimate potency easily enough is what I mean, with a fair margin of safety. IF I decide to go ahead with it. I think I might do, but I do have a few other projects to take care of however.
 
You're talking about the analogue of 6-MAM? Yeah, it'd probably be quite active. Better BBB crossing anyway. Not sure if you'd get enough valeric acid from hydrolysis (remember, 6-MAM is quite stable in vivo) to get GABAergic activity. Is valeric acid an active enough ligand anyway?
 
Seems like its not active at GABAa without the amine, although isovaleric acid is, apparently and I can obtain that instead. And yes, an analogue of 6-MAM, as this reportedly is the main product when GAA is used to acylate morphine rather than acetic anhydride. I have relatively little interest in producing heroin, I've had it enough times and actually, I don't favour it compared to morphine. Anyone know what the limit is with respect to chain length, and if double or triple bonds in the acyl chain make any difference to potency?

Seems like heroin at least is not all about acting as a vehicle for faster delivery of morphine, and it is actually splice-variant selective with respect to MOR isoforms.

Does isovaleric acid stink like valeric acid does? because that stuff is vile.
 
Isovaleric acid stinks too, but it doesnt smell like valeric acid,
It smells like butyric acid (fermented sweat-ful cloths) with a minty tint (a mint-ish smell shared between acetone, isopropanol, menthol, or things with that Y-shaped ends)

Opened a bottle in my lab once and never opened again since then lol.
 
Propionic acid is another pet hate of mine. Hydrolysing propionyl chloride is particularly vile.

Valerian root and its extracts are foul, shit knows how people use tinctures.
 
Dibutyrylmorphine is apparently less potent than morphine, while you obviously know that the prop is considered a little better than diamorphine... so it doesn't really seem like it would really give you more potency per mg if you make longer aliphatic homologues, but what it probably will do is make you opi longer lasting.

The benzoyl and nicotinoyl esters are of course known as I'm certain you are aware, and it does seem like the aromaticity is good for potency (or I should say not as pointless as an aliphatic chain of same number of carbons would be?), so if you really hate prop and don't want smelly shit, maybe there is something interesting in that direction?

6-O-Acetylsalicyloyl morph ("aspheroine" if diester) anyone? =D extra analgesia ftw

An ester of an ester, ok very esterception..

NSFW:

6-O-(2-(acetyloxy)benzoyl)morphine.png

 
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Wouldn't the diester be tricky to form, due to steric hindrance?

And believe you me, I don't hate dipropionylmorphine. Its one of my favourite of all opioids, only opium isolate, the propionyl ester of the bulk of phenolic material present in such an isolate, prepped for IV, minus codeine, I'm a big fan. I just don't like the stink of the halide. I can live with it. I mean really, its of little consequence. Its just unpleasant. I spent most of today up to my ass in ammonia, diethyl ether and more fucking ammonia. Worst of all though was accidentally sucking naphtha fumes through the tip of an E-cig accidentally wetted with a little of same. Disgusting. Well I say naptha, white spirit, just used as an inert to keep something behaving itself temporarily. Stinks though. h


As far as potency, etc goes, dipropionylmorphine beats the SHITE out of diamorphine, whilst picking up a bit of that histamine release on injection lacking in diamorphine, and its both potent, packs one hell of a rush on IV, and DAMN does it last a long time. Be lucky to get 6-7 hours of pain relief, withdrawal delay and mobility out of IV morphine. 12 easily with dipropionylmorphine, IV. Aside from opium and acylated (propionyl) 'kompot', only refined with the benefit of decent tech. The ONLY opioid thats ever hit the spot, has been methadone. And not talking cut street skag, Tried it, could give less of a shit about it. But something that can be vouched for and known not to be cut. H just doesn't. It falls short of expectactions. I'd be most curious to know if ever DPM has been assayed in tandem with morphine and H at MOR splice variants and heterodimers/higher order oligomeric receptors if they exist for MORs. Because there are notable differences in the specificity of H for certain exons present in alternately spliced MOR isoforms compared to morphine.
 
Don't know... would it help to instead just 6-salicylate morphine and acetylate both the salicylate's OH as well as the 3 of the morph after with anhydride (you don't end up with the same molecule but who cares about a 3-acetyl, might even help even extra passing BBB?).

It sure seems like a funny gimmick to me though..
 
Wouldn't the diester be tricky to form, due to steric hindrance?
Click to expand...

The 3' and 6' positions of morphine are far enough apart that sterics aren't too much of an issue, if I remember right things like dibenzoyl morphine can be made. The difficulty in making a diester usually comes from the differing acidity of the alcohol groups (2ndary allylic alcohol versus a phenol) leading to vastly different reactivities at the 3' and 6' positions.

As for the pharmacology of DPM I would expect it to be very close to diacetylmorphine, just with longer T1/2 and slightly longer time to peak effects.

Every little bit of lipophilicity you can stick onto the morphine scaffold helps affinity, as a rule of thumb. Diacetyldihydromorphine > diacetylmorphine > morphine both in potency and in BA as far as I know.

I wonder why people haven't tried mixed 6' position fatty acid esters of morphine, the same way people make time-released steroid or antipsychotic depot injections. Or maybe 3' position if you want them to be inactive until the ester is cleaved.
 
By fatty acid do you mean carboxylate esters generally, or given the context, long-chain beasties such as a very long chain such as for instance, decanoate and a shorter este on the business end? so as to increase lipophilicity and give the resultant mixed ester both as much potency as possible?

DPM is indeed longer acting than morphia or than (real, uncut) heroin. VERY significant difference in both time of effect and potency in weight terms. And contrary to wikipedias article on it, it is NOT slower (IV route) than either morphine or smack. It is significantly faster in onset than H, histamine release is intermediate between the two and it stings if give IM or subcut, duration is massively prolonged, its more like methadone in that respect. Would make a nigh perfect maintainance drug for those who dislike, cannot tolerate or do not want either methadone or bupe, for any of those for whom prescription H or morphine is more appropriate or preferred. A 460-480mg IV dose of dipropionylmorphine has kept me going for what was likely a bit less than 24 hours. And it packs a monster of a rush too. That 460-480mg shot really knocked me off my feet, and it kept me going until a little after.

I love the stuff. Means the morphine I get can be made to last more than twice as long for a given weight thereof.
 
Something like a 6-palmitoyl I guess, however considering 6-butyryl is already showing a drop in potency it doesn't seem like a 6-palmitoyl actually gives you an ester active at reasonable dosages so it doesn't seem like it would matter much at which position you place the (single) palmitoyl because it would need to be cleaved anyway to yield morphine.
But seems fine, I very much doubt that many other LAI pro-drugs are itself active, or that they are generally meant to be.

A shorter ester on the business end yeah sure it would increase lipophilicity but it is likely to be cleaved anyway on a *much* shorter timescale, I don't know whether after the short ester is cleaved the metabolite would dissipate from the brain because of an equilibrium or if it lingers because it is not taken up quite as well in the BBB membrane - an interesting question, likely the long ester makes it plenty lipophilic anyway?

Definitely no long ass diester afaik, because that would sort of complicate and multiply your kinetics and you might be looking at an unreasonable depot?
 
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I might just try the valeroyl/isovaleroyl ester(s),

Although coming first methinks will be that alpha-chloromorphide I posted a thread about, since its quick, should be easy and to boot; a 10mg morphine-100mg (potency-wise) increase would be most gratifying=D

And theres always cat-H and desomorphine. As the bad reputation it now has is solely due to the nasty swamp cooked up by russian addicrssssssss as 'krokodil'. There should be nothing wrong with the actual drug itself. Thats due to the toxic mixture of red P, iodine, NP solvents and acidic products present as rxn byproducts is it not, and would be a million miles removed from pure desomorphine, no?

How much stronger is desomorphine itself compared to morphine?
 
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Dose-by-dose it is eight to ten times more potent than morphine. Its pretty bad tho because it has a very short duration. Only lasts 2 - 3 hours


 
Does anyone remember the thread on zoklet where "bunghole" synthed and bioassayed "Russian magik" dihydrodesoxymorphine"?

I have it saved on my computer somewhere. It sounded very legit.
 
Well, in the case of desomorphine, its only being considered for testing, not conversion of all available alpha-chloromorphide. Because the couple of BL trip reports on desomorphine make it sound like one hell of a euphoriant, with a peculiarly long rush when injected, several hours according to one user here. And then a sudden and abrupt drop-off to near zero effects; this abrupt cessation of effect. Which makes me think, after testing on its own, a mixture with dipropionylmorphine would be ideal, due to the extremely long duration of action of the latter.

Sekio-sort of. There are two primary reduction products of alpha-chloromorphide. One is dihydrodesomorphine-D and the other is tetrahydrodesomorphine-D. There can be varying proportions present of a dimeric product on reduction with more active catalysts. Pressurized H2 is not required, but reflux of alpha-chlorocodide in EtOH or alpha-chloromorphide in EtOH respectively, with extremely active catalysts such as platinum black or colloidal Pt tend to give more dimer. This can IIRC be cracked to the original compounds (the chlorocodide/chloromorphide. Need to prepare some Pd/C or colloidal Pt, or plad black and have a look. Seems like the more active the catalyst and the faster the speed of reduction the more dimer is formed.

There are several desomorphines, it seems, IIRC its A,B,C and D.
 
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