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A few molecule-structure opioid questions.

'Rush' (or like the Brits say 'Flash') is not limited to one experience. There are thousands of chemicals used to produce the effect IDU's call the 'rush'. One example of a rush is the intense histamine reaction from an injection of Morphine or certain semi-synthetic opioids.

If Histamine were the only cause for a 'rush', why do Anti-Histamine drugs cause a 'rush' when they are injected with an opioid (or sometimes just by themselves)? By their very nature they suppress Histamine release, so the rush caused by these chemicals works by a different mechanism than Histamine releasing drugs.

Also, not all rushes are pleasurable. There are chemicals that cause what some IDU's call a 'dirty rush', an intense, rapid physiological change following an injection that isn't pleasant.

Plus there are stimulant and depressant drugs that cause a rush when injected, so it can't be strictly related to how a chemical effects the CNS. And many of the chemicals that cause a rush when injected are completely inactive; they do not effect the CNS at all.

It's a very complicated topic, and science generally doesn't have the answer as to why chemicals like Lidocaine, Quinine, Procaine, Diphenhydramine, Cyclizine, Clonidine, Hydroxyzine, etc etc etc create this kind of sensation either when they are injected alone or in combination with certain other chemicals. Some think combinations create new chemicals (like the discovery of cocaethylene when alcohol and cocaine are combined) that are not yet known.
 
Well, the *Caines, to a greater or lesser extent, all produce some DAT blockage. IIRC, Lidocaine was self administered by primates.

The rush is caused by your receptors filling very rapidly. It makes sense that rapidly antagonising histamine receptors produces immediate effect.
 
Another question on topic:

Could Hasubanans be used like Morphinans as a basis for opioid type substances?

I also found an Morphinan like chemical, but not a Morphinan or Hasubanan (if it was a Hasubanan it didn't say it was, I can't find it using that search term) that was found in an east asian (Chinese, Japanese or both) tree or herb. It was said to have analgesic properties and properties similar to opiates being very similar in structure to morphine. This was on Wikipedia and it was more than a stub article, but now for the life of me I can't find the page again using the search function, I've tried for three days, any help? I was interested in asking about this chemical in particular, but can't find it now. It was not hasubanan or hasubanonine: it looked a bit more like hasubanan with more actual similarity to morphine.
 
I) The idea is not to acetylate. Acetylation is only applicable to morphine. You want to increase potency and how to do so depends on a particular substance. You mention oxycodone.

Oxycodone of course can be tweaked to oxymorphone which is usually considered 15 times the potency of oxycodone.

The process by which this is done is not acetylation but O-demethylation. You need to specifically demethylate the methoxy group without changing any of the ether linkages elsewhere on the target.


There are 4 ways that I know of to do this. The easiest way, and we are not discussing synthesis, is to use boron trichloride in the presence of chlorobenzene. It is not for the novice, but with practice it can be mastered.


The problem though is this: With a 15 X increse, and the maybe 60% yield, is it even worth it? Then, until it is mastered a yield of about 20% is more than likely, if the synthesis is even succesful.

so, if you had access to ALOT of oxycodone it might be a good thing to try, but to each their own.

II) Maybe it is the whole English thing (it not being my best language), but this question and your next and last one seem to be focused on histamine release because you believe histamine release to be strongly linked to the so called "rush," yes?

If so, it is not. The "rush" relates to the degree of onset, or in more specific terms, how rapidly it links to your receptors. To gain a better "Rush," you do not want histamine release you want increased lipid solubility.

Heroin is attractive because it increases the lipid solubility of morphine by about 3.33 X, requiring 1/3rd the amount of morphine to achieve morphine's psychoactive effects. In addition, it does so much faster (and efficient) at crossing the Blood to Brain Barrier (BBB) which of course is another way of discussing increased lipid solubility.

I will not get into histamine release because unless you are really interested it as a scientific subject, or avoiding it which is actually a smart idea, it is not a wortwhile subject (to me).

Good luck.
 
Nagelfar said:
Another question on topic:

Could Hasubanans be used like Morphinans as a basis for opioid type substances?

I also found an Morphinan like chemical, but not a Morphinan or Hasubanan (if it was a Hasubanan it didn't say it was, I can't find it using that search term) that was found in an east asian (Chinese, Japanese or both) tree or herb. It was said to have analgesic properties and properties similar to opiates being very similar in structure to morphine. This was on Wikipedia and it was more than a stub article, but now for the life of me I can't find the page again using the search function, I've tried for three days, any help? I was interested in asking about this chemical in particular, but can't find it now. It was not hasubanan or hasubanonine: it looked a bit more like hasubanan with more actual similarity to morphine.
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Take these kinds of infrences with a grain of salt. I have an artsy culture magazine on my bookshelf that dedicated an issue to international drug use; on a page that lists obscure drugs, venom from a species of Cobra snake is listed as having 'Heroin-like euphoria when injected' (I can say though that the rest of the magazine had very interesting and true articles, aside from this one questionable, ridiculous statement).
 
DJ: Wih heroin versus fentanyl it comes down to, mostly, duration. Fentanyl (excepting analogs which can be as short as 10 minutes) is about 2 hours versus heroin's (up to but usually shorter by 2 h.) 8 hour duration.


Imagine fixing every hour. Not pretty.
 
Tchort said:
Take these kinds of infrences with a grain of salt. I have an artsy culture magazine on my bookshelf that dedicated an issue to international drug use; on a page that lists obscure drugs, venom from a species of Cobra snake is listed as having 'Heroin-like euphoria when injected' (I can say though that the rest of the magazine had very interesting and true articles, aside from this one questionable, ridiculous statement).
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No this one had a chemical image and everything, one could tell it was closely related and it cited some lab research into it and it's ancient use in the east as an analgesic. I'm really interested into the associated character of this if anyone knows what it is I'm talking about. Found the page only a few days ago and cannot no matter what now, it had a plant genus page and a molecule page for the molecule / chemical name itself. I think some obscure opioid page linked to it.
 
We are infested with cobras here. I wish it was euphoric hahaha...Actually, we DO have plenty of psychoactives as you will in any tropical place but cobra venom is not one of them. Exactly why I post on a HR site, stupid articles like that.


It does have , when treated, a medicinal value. The tribespeoples here use snake venom for a variety of traditional medicines. In fact, it is a whole speciality with special shamane. I will not go near it of course.

My greatest frear? It is not the 7 insurrections on this island, one of which has me boxed in on 3 sides as I post this, itis putting on my boots and getting a cobra or scorpion sting, the cobra will kill me though. The nearest antivenom is about 300 klicks south of me.
 
Heck, I remember when the researcher here was pushing snail venom (which they have since developed and patented in the US). Everybody was mistakenly thinking that it was going to be a valuable opioid. they read the comparison in analgesia (to morphine) and their braink thinks psychoactivity. If only it were that simple.
 
Found it, finally: Sinomenine. It looks like a hasubanan but it's said to be in fact a morphinan. I wonder if it could be used as a basis for a more active opioid?
 
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Not unless you get an isomer fairy on it. It's dextro-rotary; all of these dextro-morphinans are inactive as opiates.

Even dextro-morphine.
 
Hammilton said:
Here's a question- on open chain opiates like methadone, is there any known reason why alcohol groups on the quaternary carbon render them inactive (or is this not always true?). I'm thinking of trihexyphenidyl and why it's inactive.
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The quaternary carbon in methadone is fully substituted, so you can't put an hydroxy group on it

Where the tertiary nitrogen is contained in a piperidine ring is it always true that it is only active where the 2-carbon chain at least partly composed of that ring (instead of connecting to the nitrogen and being seperate, as in trihexyphenidyl)?
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Directly replacing the dimethylamine part of methadone with a piperidine group gives dipipanone

'Rush' (or like the Brits say 'Flash')
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Do we? I've never heard it called that, everyone I know refers to it as the 'rush' :D
 
The quaternary carbon in methadone is fully substituted, so you can't put an hydroxy group on it
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Obviously, and if you could, there'd no longer be a quaternary carbon- hence the 'like' ;) Leaving the phenyls unaltered, I mean.
 
Hammilton said:
Not unless you get an isomer fairy on it. It's dextro-rotary; all of these dextro-morphinans are inactive as opiates.

Even dextro-morphine.
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So sinomenine is dextro-rotary, though it says it has some analgesic effects, does that mean if it were levo-rotary it'd have a completely different innate property or be even more potent than morphine possibly? If dextro-morphinans are inactive as opiates are there anything they are active as? Could any of the hasubanans be used like morphine?
 
If they're not dextro-rotary, quite likely.

Probably as dissociatives- that's what DXM is, of course.

Sinomenine's analgesic effects are thought to be the result of histamine release, not mu agonism.

IIRC, dextro-morphine can be used with morphine to prevent tolerance. How or why, I dunno.

I doubt it'd be more potent.
220px-Sinomenine.png


Aren't these 6-oxo-C7-C8 unsaturated generally rather weak or inactive? Those methoxy groups bode poorly for affinity, too.
 
dread said:
I have it now... the perfect opioid.

View attachment 6359
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By the way: Is this something theoretical? Which of the opiates is this most closely related to? It looks like dipropanoylmorphine but the ends are different, what is the purpose of that? Wouldn't it be less effective for the same reason 6-MAM is more effective than heroin?

Would the 'rush' be prolonged if the different complexities of morphine prodrug types were administered as a polydrug at once by how soon they each activate? for example an administration of: 25% morphine, 25% 6-MAM, 25% heroin & 25% dipropanoylmorphine; would that cause the subjective effect of an increased duration "rush"?
 
No, it's a 3-acetyl-6-propanoyl-14-ethoxy-dihydromorphine.
And it's purely theoretical as far as I know.

But the idea would be that the hydroxy in 3-position would get exposed first, having the lighter acetyl group, thus giving a fast onset, coupled with high potency from the 14-ethoxy and a long activity due to the saturated 7-8 bond... Also with good lipophility since no hydroxy-groups are exposed.
 
Would the 'rush' be prolonged if the different complexities of morphine prodrug types were administered as a polydrug at once by how soon they each activate? for example an administration of: 25% morphine, 25% 6-MAM, 25% heroin & 25% dipropanoylmorphine; would that cause the subjective effect of an increased duration "rush"?
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There is evidence that simultaneously injecting different opioids together does impact the subjective effects of the rush, like intensity, particular reactions (pins & needles for ex), duration, etc. It's fairly common. Addicts have experimented with this for decades, combinations of Dilaudid + Heroin, Morphine + Heroin, Oxycodone + Heroin, etc are fairly common. I've always fantasized about either Dextromoramide or Ketobemidone + Morphine or Heroin. Too many strong opioids would probably be too muddled to tell the difference. A strong synthetic opioid that has an intense rush combined with either Morphine or a semi-synthetic derived from Morphine (Heroin, Nicomorphine, Desomorphine specifically). Two different flavors of intense, pleasurable rush. I'm probably overemphasizing the euphoria, any of these combinations would probably in practice be impossible to distinguish from Hydromorphone + Heroin which is done often.
 
Wow, does anybody remember some of the topics we covered before the site was reset to this point for this thread? I remember asking about the degree of potency of the different additions to morphine which was yet to be answered i.e. acetyl < propanoyl < etc. and we also discussed that the acetyl links on heroin were freely rotatable etc. and I know I asked a few more questions.
 
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