halomorphides, dihalomorphides

[Limpet_Chicken]

According to wikipedia, alpha-chloromorphide is some 10x the potency of morphine.

And would be a snap to make, although selectivity might be a bit of a pain, to selectively chlorinate only the 6-position and leave the 3-OH untouched. Although the 3-position is known to be less reactive when the preparation of 6-MAM is performed with a glacial carboxylic acid (inc. of course other 6-monoacylated derivatives. Would this extend to halogenation nucleophilic reagents?

What I am curious about is if the initial step in the rissian krokodil synthesis where SOCl2 is employed (batteries, I believe they get theirs from. Beggars (literally quite possibly) cannot, as they say, be choosers. Although nor I suppose, can pre-teens and young teens (I got mine that way, from large thionyl chloride/lithium batteries) not that I was using it for knocking up any batches of lovely, tasty flesh-rotting smack on morphine as opposed to codeine results in the positional isomer beta-chlorocodide (assuming this IS the correct nomenclature? wikipedia has no entry for beta-chlorocodide)

How do other halides, fluoro included, but primarily interested in bromine and iodine, and other highly electron-withdrawing groups such as nitro or trifluoromethyl affect potency? because chlorine at ~10x potency of morphine would make it even more potent than dipropionylmorphine, although it would have quite some work to do to improve on dipropionylmorphine. Although that is not saying very much, it is afterall pretty much the king of any opiates I've ever had the chance to try.

It seems like the halomorphides have primarily been used as synthetic intermediates on the way to other opioids with little history of human use.

Anyone know more on the pharmacology of these, in particular potential for euphoria, potential for addiction and physical dependence, known toxicity, analgesia, any biased agonism, and speed of tolerance development, general potential for tolerance?

 

[serotonin2A]

I think everything written about SOCl2 is just speculation based on published routes for desomorphine synthesis. My recollection of krokodil production is that it is basically a one pot reaction and the same reagents that are used to reduce codeine to desocodeine can also demethylate the desocodeine to desomorphine.

 

[aced126]

According to wikipedia, alpha-chloromorphide is some 10x the potency of morphine.

And would be a snap to make, although selectivity might be a bit of a pain, to selectively chlorinate only the 6-position and leave the 3-OH untouched. Although the 3-position is known to be less reactive when the preparation of 6-MAM is performed with a glacial carboxylic acid (inc. of course other 6-monoacylated derivatives. Would this extend to halogenation nucleophilic reagents?

What I am curious about is if the initial step in the rissian krokodil synthesis where SOCl2 is employed (batteries, I believe they get theirs from. Beggars (literally quite possibly) cannot, as they say, be choosers. Although nor I suppose, can pre-teens and young teens (I got mine that way, from large thionyl chloride/lithium batteries) not that I was using it for knocking up any batches of lovely, tasty flesh-rotting smack on morphine as opposed to codeine results in the positional isomer beta-chlorocodide (assuming this IS the correct nomenclature? wikipedia has no entry for beta-chlorocodide)

How do other halides, fluoro included, but primarily interested in bromine and iodine, and other highly electron-withdrawing groups such as nitro or trifluoromethyl affect potency? because chlorine at ~10x potency of morphine would make it even more potent than dipropionylmorphine, although it would have quite some work to do to improve on dipropionylmorphine. Although that is not saying very much, it is afterall pretty much the king of any opiates I've ever had the chance to try.

It seems like the halomorphides have primarily been used as synthetic intermediates on the way to other opioids with little history of human use.

Anyone know more on the pharmacology of these, in particular potential for euphoria, potential for addiction and physical dependence, known toxicity, analgesia, any biased agonism, and speed of tolerance development, general potential for tolerance?

I'm not too sure the quarternary carbon is off much importance to opioid SAR. The more polar groups are much more significant factors that affect the affinity of a compound to the mu opioid receptor. For example, several open chain opioid analogues exist, some with several times the potency of morphine itself (e.g. fentanyl), implying that the rings in morphine are not THAT important. We would call morphine a rigidified structure, and rigidified structures often have incredibly high affinities at receptors because they exist in a conformation close to the conformation an open chain analogue would bind to in the receptor. If an open chain analogue has to change its conformation to one different from its energy minimised conformation, then it is less likely to bind as it spends less time in higher energy conformations. So fixing a drug to a certain conformation (often done by nature with many toxins) can result in very strong binding. I think that it just so happens that the conformation of morphine is pretty good, but nowhere near the optimal conformation for strongest binding to mu. We know this because there exist several open chain opioid analogues with several times the potency of morphine (e.g. fentanyl analogues and methadone analogues to name a few). This suggests that functional groups play a much greater role in SAR than shape of molecule. I will briefly discuss the main points in opioid SAR.

The nitrogen in morphine plays an important part in SAR. First of all, if the nitrogen has 4 alkyl groups on it, and is thus charged (for example in methylnaltrexone), then it is too polar to cross the blood brain barrier and will have no psychoactive effects. It still binds strongly to peripheral opioid receptors, and this tells us that when the opioid is bound to the receptor, the nitrogen is charged (and thus protonated in the brain) when it binds to mu. It forms an ionic bridge with a negatively charged amino acid residue (such as aspartate). It's observed that making the nitrogen secondary in morphine (https://en.wikipedia.org/wiki/Normorphine) significantly reduces potency. I think this is because normorphine can act has a H-bond donor, which disrupts the ionic bridge by changing its angle or something. So a tertiary nitrogen is important for good opioid activity. And as you will see, almost all opioids in clinical use have a tertiary nitrogen.

The 3-OH group in morphine plays an important role in binding. It acts as a H-bond donor. Adding a methyl group at this position (codeine) significantly reduces potency.

The 6-OH group in morphine is not involved in binding very much at all and is not significant. It can be replaced by (long) alkyl substituents and still retain potency. Thus one can add lipophilic substituents on this group, like in heroin, to increase concentration of the blood reaching the brain.

The ether bridge is not important for binding to mu, but removing it increases the time taken for the blood to reach the brain. Ethers are weird in that they slightly increase polarity but not massively. Diethyl ether is a non polar solvent, of course. I think, to cross the BBB most effectively, you need in general a pretty lipophilic compound, with a few hydrophilic spots to stabilise it initially as it approaches the phosphate head (someone correct me if I'm wrong, I'm not too sure on all that logic). Ethers suit this purpose best. Alcohols, less so, and carboxylic acids cross the BBB in very small proportions. I think it is something to do with ethers not having a labile hydrogen, and thus it is not that unfavourable for them to be surrounded completely by alkyl chains in the phospholipid bilayer, at least less unfavourable than alcohols and carboxylic acids.

Hydrogenating the double bond in morphine increases potency. It relieves some strain on the molecule, and lets the molecule conform to a slightly more optimal binding conformation. More evidence that the morphine conformation is by no means the best opioid conformation for strongest binding.

Adding an alcohol group on carbon 14 increases potency (e.g oxycodone, oxymorphone). This is likely because this group acts as a H bond donor or acceptor while bound to the receptor.

You can exploit the fact that the 3-OH position is aromatic and thus is much more acidic (maybe around 10^5 times more acidic) and the 6-OH position. The 3 position isn't necessarily less reactive. If the 3 position is deprotonated and the 6 isn't (need a pH of around 12 maybe) then the 3 position will react as the nucleophile preferentially, as it is deprotonated but the 6 isn't. Likewise if you want to perform the chloro substitution you desire, neutral conditions should result in good chemoselectivity.

Chloromorphide has the same stereochemistry as morphine, so performing this reaction with other reagents like PCl5 will result in inversion of that stereogenic centre. However, I still think this won't affect potency much as that position really doesn't play that big a role in the pharmacodynamics, as mentioned in my old post above. Nevertheless, SOCl2 will retain stereochemistry as the reaction proceeds via an SnI pathway (unless using a suitable Lewis acid, no ion pair can then result and Sn2 occurs).

 

[Limpet_Chicken]

It (the three position) can play a role in things, such as morphine-3-glucuronide compared to the equivalent M6G. The former is a proinflammatory toxin, and IIRC a convulsant also. And IIRC, 3-monoacetylcodeine is a proconvulsant agent, and possibly, can't remember how, but 3-MAM is toxic in some way. Morphine exhibits proinflammatory toxic effects especially if administered intraspinally, this is thought to be the reason why.

I take it that acidic environments would thus, as per your explanation about stereochemistry, would foster selectivity?

Although now that you mention it....that might not be ENTIRELY such a shitty thing, afterall. Because aren't the dextro-isomers NMDA antagonists, of most of the morphinan type opioids? dextromorphine would be most interesting to try.

 

[aced126]

It (the three position) can play a role in things, such as morphine-3-glucuronide compared to the equivalent M6G. The former is a proinflammatory toxin, and IIRC a convulsant also. And IIRC, 3-monoacetylcodeine is a proconvulsant agent, and possibly, can't remember how, but 3-MAM is toxic in some way. Morphine exhibits proinflammatory toxic effects especially if administered intraspinally, this is thought to be the reason why.

I take it that acidic environments would thus, as per your explanation about stereochemistry, would foster selectivity?

Although now that you mention it....that might not be ENTIRELY such a shitty thing, afterall. Because aren't the dextro-isomers NMDA antagonists, of most of the morphinan type opioids? dextromorphine would be most interesting to try.

Dextro isomers of opioids would be expected to not have an opioid activity anyway, because of complete reversal of stereochemistry of an extremely constrained molecule. However as long as the main part of the molecule has the right stereochemistry, I don't think what's on the 6 position really matters that much. PK differences due to the 6 position tend to play a much bigger part in the properties of the drug.

The stereochemistry explanation wasn't really related to the selectivity. Having a lewis acid inverts stereochemistry, giving you the wrong diastereomer that you want. The selectivity arises from increased nucleophilicity of the 6 hydroxyl group. In fact I just realised that the 3 position won't react at all because it is a phenol. The carbon is sp2 and any nucleophile cannot access the C-O antibonding orbital (as it is in the plane of the ring). An intimate ion pair also can't result because a phenyl cation with an empty sp2 orbital is extremely unstable. Yet in very rare cases can these phenyl cation intermediates be regenerated. For example, exposing a diazonium salt to temperatures above 10 degrees celsius will result in N2 departing as a leaving group. The resulting intermediate is extremely susceptible to nucleophilic attack and is instantly attacked by a water molecule, forming a phenol. However, at lower temperatures other nucleophiles could be used. For example H3PO2 is able to replace the diazonium moiety with hydrogen. Nucleophilic substitution can occur (attack on pi antibonding orbital, which is orthogonal to the plane of the ring) if there is an electron withdrawing group ortho or para to the leaving group (SO2 in this case) but this is not the case here. In fact the leaving group itself should be electron withdrawing as well, to increase the rate determining step of addition of the nucleophile to the ring, but this is not the case here as the chlorosulphite is conjugatively electron donating.

tl;dr SOCl2 achieves complete selectivity because electron rich aromatic rings don't undergo nucleophilic substitution.

 

[Limpet_Chicken]

Oh I read it. I'm actually interested in chemistry (and physics, and especially mycology and biotech)

 

[sekio]

what about 8-bromiomorphide?

or do I need to make & bioassay?

 

[Limpet_Chicken]

Well its probably active if the chloro substituent is. But your question is just the same as something I myself wanted to know. My money is on make and bioassay.

If you do it before my resupply of thionyl chloride arrives, go for it and test it, if you don't get the chance before it does, I'll give a heads up on the chloro analog. Won't be able to get thionyl bromide to test the bromo-homolog in anything like prompt time, not before the end of the month can I order any SOBr2. I could of course obtain ordinary vanilla thionyl chloride via other channels, but the channel I use to obtain my more difficult items (E.g oxalyl chloride, PCl3 and PCl5, various hydrides, cyanide salts) is away currently on vacation. So for a little while I won't have access to things that have at most, rare and niche uses and very little trade outside established businesses. Not that many of them care, its just that those that cater primarily to actual real people rather than incorporated names have little incentive to carry things their target demographic would rarely ever use.

I have a question regarding stereochemistry of morphine alkaloids. During a halogenation of one of the terminal alcohols of morphine for example, would the large, bulky triple Ph-phosphonium halide formed as an intermediate/transient state during the Appel rxn (no more needs be said on that) invert stereochemistry of morphine?

Actually, the thought of using say, PCl5 or PC3 to perform the chlorination to chloromorphide and hydrogenation to D-desomorphine actually sounds like good stuff to be honest, with the premise being to sacrifice the opioidergic agonism in favour of gaining potent NMDA antagonists. I've yet to look but I presume that for both the unnatural isomer and for racemic morphine and derivatives of similarly inverted stereochemistry from the naturally ocurring isomer of morphine there will be few if any reports here.

 

[Limpet_Chicken]

Well its probably active if the chloro substituent is. But your question is just the same as something I myself wanted to know. My money is on make and bioassay.

If you do it before my resupply of thionyl chloride arrives, go for it and test it, if you don't get the chance before it does, I'll give a heads up on the chloro analog.

 

[aced126]

Well its probably active if the chloro substituent is. But your question is just the same as something I myself wanted to know. My money is on make and bioassay.

If you do it before my resupply of thionyl chloride arrives, go for it and test it, if you don't get the chance before it does, I'll give a heads up on the chloro analog. Won't be able to get thionyl bromide to test the bromo-homolog in anything like prompt time, not before the end of the month can I order any SOBr2. I could of course obtain ordinary vanilla thionyl chloride via other channels, but the channel I use to obtain my more difficult items (E.g oxalyl chloride, PCl3 and PCl5, various hydrides, cyanide salts) is away currently on vacation. So for a little while I won't have access to things that have at most, rare and niche uses and very little trade outside established businesses. Not that many of them care, its just that those that cater primarily to actual real people rather than incorporated names have little incentive to carry things their target demographic would rarely ever use.

I have a question regarding stereochemistry of morphine alkaloids. During a halogenation of one of the terminal alcohols of morphine for example, would the large, bulky triple Ph-phosphonium halide formed as an intermediate/transient state during the Appel rxn (no more needs be said on that) invert stereochemistry of morphine?

Actually, the thought of using say, PCl5 or PC3 to perform the chlorination to chloromorphide and hydrogenation to D-desomorphine actually sounds like good stuff to be honest, with the premise being to sacrifice the opioidergic agonism in favour of gaining potent NMDA antagonists. I've yet to look but I presume that for both the unnatural isomer and for racemic morphine and derivatives of similarly inverted stereochemistry from the naturally ocurring isomer of morphine there will be few if any reports here.

Remember, if using PCl5 to chlorinate morphine, you don't generate chloromorphide per say, as defined on wiki, but you generate the other diastereomer. Of course this doesn't matter if you want to hydrogenate to desomorphine.

From a quick wikipedia skim, the Appel reaction goes via Sn2 for primary and secondary alcohols, so it would invert stereochemistry in the case of morphine. For tertiary alcohols a carbocation is formed and the Cl- attacks the less hindered side. In many constrained structures, forming a planar carbocation is not sterically possible, so these substrates do not undergo Sn1 type reactions.

 

[Limpet_Chicken]

I was just thinking about that actually. Already got it in mind to try the Appel rxn out actually, on the thiazolethanol cleavage fragment of thiamine, to see if I can get it working and out there so to speak on some other forums for people who have trouble getting thionyl chloride.

And yes, desomorphine had already occurred to me, its meant to pack one hell of a rush isn't it? indeed it would be a shame to create the halomorphide and NOT reduce some of it, no? not, of course using the ugly as sin krokodil-style RP/I reduction scheme or its relatives.

 

[Limpet_Chicken]

Well, we should know more about the bioactivity of alpha-chlormorphide quite soon. Hopefully within a few hours at most. Probably not desomorphine...not yet anyway. But I won't ignore the matter.

Also-Anybody know if morphine-6-sulfide is active? or the corresponding selenide?
And likewise for the codeine homologs, and alpha-chlorocodide-is it active in its own right, or must it be first biologically converted to alpha-chloromorphide?

 

[aced126]

Well, we should know more about the bioactivity of alpha-chlormorphide quite soon. Hopefully within a few hours at most. Probably not desomorphine...not yet anyway. But I won't ignore the matter.

Also-Anybody know if morphine-6-sulfide is active? or the corresponding selenide?
And likewise for the codeine homologs, and alpha-chlorocodide-is it active in its own right, or must it be first biologically converted to alpha-chloromorphide?

The 3-OH position is quite necessary for good binding, so a-chlorocodide is probably a prodrug. Morphine-6-sulphide is probably active.

 

[Limpet_Chicken]

Alpha-chlorocodide probably is.

The morphide is ready. Chlorination has finished, just quenching with a little water, and evaporating off, then will extract, neutralize if needs be and prepare it.

This should be interesting.

I don't really have enough to try dehydrohalogenation w/colloidal Pd or plad cat, not currently anyhow. But a 10mg morphine to >100mg change in potency is to say the least nothing to be sniffed at.

 

[Limpet_Chicken]

Whoa! this is some WEIRD shit.

Prepped 50mg for IV, came to a little over 5ml of liquid, so shot as much as possible of that, using a 5ml barrel, had to leave a little bit back in the prep vessel, which was plugged with the rest of it in there already. Most was IV'ed.

Onset is rapid, immediate increase in force and rapidity of heartbeat. Its strong, immediate rush, much faster onset than morphine, the rush hit me before I'd had time to get half the solution in there. Much less histamine release than morphine too. Morphine stings like a bitch pulling the needle out when a little bit extravasates. And the histamine release usually leaves welts right up my arm. The alpha-chloromorphide didn't, in fact barely even a slight mark over the IV site. Rush was medium-strong, but very, very quick to occur. Made my hands shake, which is why I had to pull out and plug the rest.

But this is VERY different from morphine. Not in the least sedating. Strong, yes. But its a stimulant, opioidergic certainly, but its not like any other opioid I've ever tried, other than kratom. And only old kratom at that. Which makes me think that alpha-chloromorphide might have significant affinity as a DOR agonist.
Euphoria..hm, undecided as yet but definitely present. But this is SO different from morphine, heroin or dipropionylmorphine that I actually wondered if I'd inadvertently chlorinated pseudoephedrine or methamphetamine rather than morphine.

I think now I'm going to experiment and take another shot, but fucking hell this is odd shit. More like a classical psychostimulant with opioid effects. And feels very reminiscent of kratom, only a great deal stronger. I'd barely have noticed 50mg of morphine, 500 yes, that I would be content enough with, likewise double that, so I think I'll give it another go.

And it tastes like absolute SHIT. Gave a little crystal a taste after running the rxn, adding H2O to quench the leftover unreacted SOCl2 and evaporated, fucking rank as a turd floating down the Styx. And it is BITTER, morphine is, sure, but nothing like this!

I am not sure what to make of alpha-chloromorphide. Once I have enough to try again, I'll give the catalytic dehydrohalogenation a whirl and see how that goes. Really, don't know what to think of it, I feel like I SHOULD be nodding, but instead I feel jacked up, as though I'd just taken a belt of methamphetamine or amphetamine. Strange stuff.

 

[Limpet_Chicken]

Update-more concentrated solution stung like a fucking bastard.

More than morphine, although possibly not due to histamine release as the welts raised are localized, instead of spreading right up my arm, to the elbow, which is what happens if I do a shot of 0.5-1g morphine.

Did a further dose, a little over 100mg, I'd estimate 130-140. Again this is very, very different from conventional opioids. It DOES alleviate withdrawal from MOR agonist opioids, but effects are just so far removed from say, morphine, codeine, DHC, H, dipropionylmorphine, meptazinol or anything else I can think of, save only some, but not other batches of kratom.

The second dose caused some fine tremor in the hands, immediate muscle fasciculations (may not be due to the drug, as they were in my arse cheek of all places) and minor twitching of the extremities. I think it would be a very good idea to be extremely careful with alpha-halomorphides. In case, as I theorize, they, or alpha-chloromorphide in particular is indeed a strong delta opioid agonist. Some of them, although not others, cause seizures at higher doses. I believe this must be due either to subtype selectivity for DOR1 or DOR2, or potentially biased agonism. Although my money is on the former. Which subtype I don't know.

Also, this is an appetite suppressant, and a strong one. Almost anxiogenic. But not. Almost as though it was anxiogenic and anxiolytic at the same time. Appetite suppression is quite powerful, I was pretty hungry before and now I feel like I could barely eat. Although at the same time I have a major craving for candy and other sweet things. Might see if I can manage an ice cream after I've had a cigarette. Unusually for an opioid the alpha-chloromorphide does not, on the face of things, make me crave tobacco like crazy. morphine or prope-dope both do. Although it does make me REALLY want a dose of a definite, and strong MOR agonist. Usually I want to chain smoke rollups on opioids, but this, while I've not had one yet, doesn't much.

 

[Limpet_Chicken]

Update-Still going full on, no decrease in effects noted.

Slight headache developed a little while ago, 20 minutes to a half hour.

Headache resolved, and started to feel a lot more positive after conversion of remaining morphine to prope-dope and having a belt on that. Unsurprisingly, similar effects to other times its been used, modulated of course by the peculiar-feeling stimulating properties of alpha-chloromorphide. Located a shallow vein in my leg and hit up, dose unknown, but even had there been no synthesis whatsoever of the alpha-chloromorphide, the quantity of morphine present, and assuming a quantitative yield during the acylation with propionyl chloride, would quite simply, not been capable of overdosing me. just under 400mg, taking wikipedia citation for the potency of the acetyl diester as between 2x-4x the potency of morphine sulfate, (which end of the scale do people think it is, btw?) and prope-dope is, from experience similarly more potent than H, that would make between 800-1200mg morphine, and double that 2-2.4g, I think most likely I'd survive that, although it might make me pretty thoroughly nauseated and itching like crazy, potentially throwing up too, and overloaded, as for some reason conventional MOR agonist opiates can at very high doses (1.5g-1750mg make me prone to overloading, although adrenergic autoreceptor agonists help prevent or reverse this.

Anyhow, whilst I was on the fence really as to whether or not I wanted the effects of the alpha-chloromorphide to continue, although more yes than no, but just about; having that shot of prope dope did the trick and aside from of course, giving me a really very pleasant rush it helped ease the overstimulating effects of the alpha-chloromorphide at the dose taken.

I don't know about 10x the potency of morphia (alpha-chloromorphide), if it is then the drug gives relatively lesser rush, but much quicker in onset. Still gives some just not to the same degree as...errm...well, it actually is very difficult to estimate an equipotent level of a conventional opioid to this drug. Mainly because the effects are just so different in their basic nature.

Also, it appears to be quite a bit less effective as an analgesic than morphine or prope dope.

I am looking for any information on it that suggests it may be a DOR agonist. Anyone happen to know one way or the other?

 

[Tryptamite]

Very very interesting.

Id often wondered about morphides.
Is beta-halo-morphide simply the same but halogenated at the 3 position where the methyl ester is in codeine??

Apparently you would have made beta-chloromorphide as 10-15% of your product. Can find source if necessary.

So still active as an MOR agonost. As in it holds off WDs?
Overstimulation I wonder what can those of us not on the spectrum take from this? Although if conventional opioids can do this to you then perhaps it is a question that isn't really so unique to this compound in particular.

How do you feel now? Be careful for goodness sake, as much as I welcome your experiments in the interest of science and for my own curiosity, I would hate to see something bad happen because of a reaction side product of some mistake or something

 

[Limpet_Chicken]

The 3-position of codeine is not a methyl ester, but a methyl ether. An ether is a compound of the general structure R-O-R where R is a carbon atom, namely alkyl, phenyl or other heterocycle, examples include EtOEt, diphenyl ether, THF, and diisopropyl ether.

Regarding overloading, that is different from excessive stimulation, and it is difficult to explain what it is or what its like to someone who doesn't already know. Conventional opioids can do it to me, but only at very high (for me) dosage levels. It would take upwards of a gram of morphine, quite a lot more in fact. before I even get close. And since I am on a prescription that aside from the morphine and oxy, includes clonidine, tizanidine, gabapentin and chlormethiazole it is suppressed very effectively.

Tryptamite, since you mention being on the spectrum vs not, I figure it is relevant to ask-are you autistic? and if you are then what strain?

Whilst I have not ran it through tests such as electrophysiological responses under patch-clamp conditions with MOR-transfected cells, I would make a pretty thoroughly educated, opioid-wise, guess as to the fact that yes, it is indeed a MOR agonist. It does hold withdrawals off, I waited for my pain meds to wear off from last nights last dose then did the alpha-chloromorphide. I was not in full-blown horrific WD, but mildly, and deliberably so to enable testing. It did indeed relieve my withdrawal at a dose of between 150 and 200mg total.

It also produced a rush, and some histamine release, as evinced by welts appearing just over the IV site and within a few inches around it. The histamine release is it seems relatively minor compared to morphine. And the fact that there IS any histamine release whatsoever, proves that there is indeed MOR agonist activity, as MORs heterodimerize with galanin-related peptide receptors, and agonism of this receptor type induces histamine release.

The stimulatory effect is very different to noradrenergic/dopaminergic releasers/reuptake inhibitor type stimulants. I've never tried a monoaminergic activity enhancer though although given the nature of the compound in question, I doubt it is one of those, and it does not feel like a histamine autoreceptor antagonist either, and definitely not like that nasty shit yohimbine. Alpha-2 antagonists and noradrenergic releasers (selective ones) quite simply, make me ill.

This is something unique, although its got a lot in common with aged kratom.

Did have a minor seizure in my sleep, but after the drug felt although it has worn off (seems fairly long acting btw), and that has been happening a lot of late, to the extent I told my GP to increase my dose of chlormethiazole as provided on prescription. (as opposed to that arising from the DIY approach) So, it may have possibly been promoted by the alpha-chloromorphide, but I don't think so, not much if at all, because these damn myoclonic seizures in my sleep keep happening anyway.

Whats the opinion of others, as to whether or not this drug is an agonist at DORs?

 

[Limpet_Chicken]

The 3-position of codeine is not a methyl ester, but a methyl ether. An ether is a compound of the general structure R-O-R where R is a carbon atom, namely alkyl, phenyl or other heterocycle, examples include EtOEt, diphenyl ether, THF, and diisopropyl ether.

Regarding overloading, that is different from excessive stimulation, and it is difficult to explain what it is or what its like to someone who doesn't already know. Conventional opioids can do it to me, but only at very high (for me) dosage levels. It would take upwards of a gram of morphine, quite a lot more in fact. before I even get close. And since I am on a prescription that aside from the morphine and oxy, includes clonidine, tizanidine, gabapentin and chlormethiazole it is suppressed very effectively.

Tryptamite, since you mention being on the spectrum vs not, I figure it is relevant to ask-are you autistic? and if you are then what strain?

Whilst I have not ran it through tests such as electrophysiological responses under patch-clamp conditions with MOR-transfected cells, I would make a pretty thoroughly educated, opioid-wise, guess as to the fact that yes, it is indeed a MOR agonist. It does hold withdrawals off, I waited for my pain meds to wear off from last nights last dose then did the alpha-chloromorphide. I was not in full-blown horrific WD, but mildly, and deliberably so to enable testing. It did indeed relieve my withdrawal at a dose of between 150 and 200mg total.

It also produced a rush, and some histamine release, as evinced by welts appearing just over the IV site and within a few inches around it. The histamine release is it seems relatively minor compared to morphine. And the fact that there IS any histamine release whatsoever, proves that there is indeed MOR agonist activity, as MORs heterodimerize with galanin-related peptide which is the mechanism for histamine release.

So anyone agree that this sounds like it might be a DOR agonist? esp. anyone who has tried a selective DOR agonist?


Thanks for the concern tryptamite.

I cannot help myself however, I am careful, but I LIVE for exploration like this. There are of course plenty of people addicted to drug use on BL. Me on the other hand am definitely addicted to pharmaceutical chemistry and biotech. I really can't help it...its just..its what I DO.

Sekio, if you do the bromomorphide, do give a report. Any idea how soon we might hear of it?


One thing you should know, is that it can for some reason which is unclear, behave differently if subjected to various precious metal catalysts at STP in EtOH or iPA. This article should be enlightening,

http://sci-hub.cc/10.1021/ja01341a051

DESOXYCODEINE STUDIES. 111.
THE CONSTITUTION OF
THE SO-CALLED a-DIHYDRODESOXYCODEINE: BIS-DIHYDRODESOXYCODEINE