Oreobeiline, so close to the morphinan skeleton.

[Nagelfar]

Oreobeiline, closer to morphine than the morphinan skeleton.

Had to edit the title: *closer* to morphine than the morphinan skeleton is. In-fact.

Oreobeiline

Real interesting. Those bentley compounds have a seven position substitution like the hydroxy on the saturated ring, just not the other on the benzene across. It's also missing that "oxygen cummerbund"

interesting compound, I think of how Bentley used oripavine that isn't found in morphine/codeine poppies, well oreobeiline is found as an alkaloid in Lauraceae, but perhaps a possible precursor in its own right.

 

[aced126]

Well its enantiomer would probably have notable mu affinity once the 3-methylether is demethylated.

This compound is more like DXM than anything, and I wouldn't be surprised if some of its pharmacology were similar to DXM.

 

[asecin]

there are way way too many topics on various novel opiates on this forum. i just dont understand this fascination with them. opiates are just bad news, no matter how many more newer ones are made, i still see them as quite the turn off. only as a dumb teen i found them enticing. i dont think any grown man should lower himself to bother discussing them and yet, on this section of the forum that is predominantly people with vast knowledge and experience find themselves going back and fourth to them again and again to such extent that im finding it unbelievable

 

[DotChem]

^ But these are probably no opiates!!! The name is kind of misleading. Not all morphinans are morphine-like with opiates activity. Only the ones with the right stereochemistry. This compound is the opposite stereochemistry of that of morphine. As aced126 mentioned, they are more likely to have similar pharmacological profile as DXM: NMDAr antagonist dissociatives with possibibly kappa agonist hallucinogenic activity + sigma agonist.

morphine-like morphinans stereochemistry:

DXM-like morphinans stereochemistry:

 

[throughthewormhole]

And besides novel opioids are neat it's ignorant folk that have issues .... Albeit things like w-18 n the like are a bit wreck less

 

[palmanita]

For me the truly intriguing point is about the stereochemistry. With (simplified) NMDA antagonism being the one (dextro) and mu agonism the other (levo) half in quite a few molecules. There appear to be interactions between the receptors itself. They can substitute for each other to some degree (you can go off opioids with dissociatives, opioids help for dissociative-induced craving and after-effects and both are antinociceptive). It's the most yin-yang like drug mechanism I know of ...?

Thinking further, could there be some differencies in the in-vivo binding and effects profile between molecules that have this stereochemistry like levor-/dextrorphanol and others that lack it, like fentanyl or ketamine?

 

[aced126]

For me the truly intriguing point is about the stereochemistry. With (simplified) NMDA antagonism being the one (dextro) and mu agonism the other (levo) half in quite a few molecules. There appear to be interactions between the receptors itself. They can substitute for each other to some degree (you can go off opioids with dissociatives, opioids help for dissociative-induced craving and after-effects and both are antinociceptive). It's the most yin-yang like drug mechanism I know of ...?

Thinking further, could there be some differencies in the in-vivo binding and effects profile between molecules that have this stereochemistry like levor-/dextrorphanol and others that lack it, like fentanyl or ketamine?

Interesting point which I always ponder over as well, however the fact is DXM and other molecules of the sort bind with weak affinity to mu receptors, so DXM couldn't alleviate opioid withdrawal directly; it would have to be via another (probably much more complex) mechanism.

Also opioids would probably help with withdrawal of just about anything

 

[adder]

In Oreobeiline B & C rings are trans while in dextromethorphan they're cis, cis-B/C l-morphinans are also the more active ones, although there are some trans-B/C levorphanol analogues that were tested and are described in Casy & Parfitt. A similar compound to oreobeiline is sinomenine which has the cis-B/C stereochemistry (just as dextromethorphan).

 

[palmanita]

For some, NMDA antagonism is enough to take away a good part of opioid w/d, I've read this too many times in experience reports to be pure coincidence and I believe that it also wasn't just luck that I could withdraw with ease after months on AH-7921, with memantine & clonidine. This combo takes away glutamatergic, cholinergic and noradrenergic rebound, the D2 agonism works against anhedonia and 5-HT3 antagonism deals with nausea. So almost anything is covered ...?

Also opioids would probably help with withdrawal of just about anything

I think the same is true for NMDA antagonists. The more I think about and experience them, the more similarities I see between them (when keeping in mind that the usual dissociative isn't a plain selective NMDA antagonist, even memantine has strong other effects like being an equipotent D2 agonist, nACh antagonism - Ketamine is an anticholinergic too and HCN1 blocker - etc).

 

[aced126]

In Oreobeiline B & C rings are trans while in dextromethorphan they're cis, cis-B/C l-morphinans are also the more active ones, although there are some trans-B/C levorphanol analogues that were tested and are described in Casy & Parfitt. A similar compound to oreobeiline is sinomenine which has the cis-B/C stereochemistry (just as dextromethorphan).

Oh yes, this is indeed true, and this is the lettering system adder is using, for clarification:

 

[Limpet_Chicken]

Whats the natural source of this compound? and does it produce the corresponding L-isomer in vivo?

 

[Nagelfar]

Whats the natural source of this compound? and does it produce the corresponding L-isomer in vivo?

New Caledonia: A ' Hot Spot' for Valuable Chemodiversity: Part 2: Basal Angiosperms and Eudicot Rosids (in Chemistry & Biodiversity 13(1):18-36 · January 2016 DOI: 10.1002/cbdv.201400389)

isolated from Lauraceae (Beilschmiedia). There is also 6-epioreobeiline wherein the 6-position methoxy is of the other orientation, but the entire configuration doesn't seem to be reversed in the alkaloids of Lauraceae.