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N-phenylethyl 14-methoxymetopon vs Sufentanil

Fertile

Fertile

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Has anyone else identified the piperidine ring of both the title compounds and noted that both of them can be considered to have a 4-methoxymethyl moiety? It's important to remember that the way a compound is drawn in 3D is a diagram rather than a map. Both of them boast very high potency and very high TIs. If you dig into the literature and search for sufentanil, earlier work states it's a potent, selective µ agonist BUT later works have demonstrated that sufentanil (but not fentanyl) is also a δ agonist.

This is merely a tiny incremental work in identification of duel µ/δ ligands that seem to be much more active thus require much lower doses and thus are safer.
 
fastandbulbous said:
Delta agonists are supposed to be quite similar to mu agonists (how to display greek letters is still beyond my abilities), so it wouldn't be a surprise if they were synergistic.
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only thing i know about delta agonists is that they are convulsants from a certain dose on.
 
fastandbulbous said:
Delta agonists are supposed to be quite similar to mu agonists (how to display greek letters is still beyond my abilities), so it wouldn't be a surprise if they were synergistic.
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That seems to be the case. Sufentanil is x5 fentanyl in potency but the LD50 is lower. MAYBE the thiophene ring has some influence.

I had imagined people selling the immediate precursor to fentanyl homologues in which the phenylethyl was substituted for another arylethyl but nope, they just alter amides.

I do not like the class. U47700 was OK but when people sell stuff that is x12000 morphine as a solution, it's dangerous because when you reach that potency, the potency actually varies from person to person so much.
I always term the N-allyl homologue of U47700 as U93951 as a joke.
 
Yes - I believe one isomer is x120 M. I think the other is the same as fentanyl i.e. x80 M. I have no idea if it alters the qualitative effects but I have avoided the fentanyl scaffold like the plague.

It seems that it's mixed activity that is most euphoric. Be it MOR agonist/NMDA antagonist or MOR agonist/DRI or ideally MOR agonist/NMDA antagonist/DRI. If only a more potent version of nortilidine existed. I DID wonder if the camfentamine scaffold could be modified. The ring would be more rigid but the amine and ester/ketone would remain less so.
 
Fertile said:
Yes - I believe one isomer is x120 M. I think the other is the same as fentanyl i.e. x80 M. I have no idea if it alters the qualitative effects but I have avoided the fentanyl scaffold like the plague.

It seems that it's mixed activity that is most euphoric. Be it MOR agonist/NMDA antagonist or MOR agonist/DRI or ideally MOR agonist/NMDA antagonist/DRI. If only a more potent version of nortilidine existed. I DID wonder if the camfentamine scaffold could be modified. The ring would be more rigid but the amine and ester/ketone would remain less so.
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Ester/ketone of camfetamine?
 
Well, I am presuming it would be an ester or reversed ester would be the most active , but with opioids, their are so many one-off cases so MAYBE an ethyl ketone or ethylsulfonyl will be the more active. With pethidine, the ethyl ketone and ethylsulfonyl have 30% the activity... but I have noted those moieties producing high activity on non-phenolic opioids.
 
Fertile said:
Well, I am presuming it would be an ester or reversed ester would be the most active , but with opioids, their are so many one-off cases so MAYBE an ethyl ketone or ethylsulfonyl will be the more active. With pethidine, the ethyl ketone and ethylsulfonyl have 30% the activity... but I have noted those moieties producing high activity on non-phenolic opioids.
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Sorry if I'm being slow on the uptake, bit an ester/reversed ester attached where on the bicyclic ring (or have I not even got the right stick, never mind the right or wrong end 😁)
 
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I didn't check the absolute isomerism, I just ensures it was clearly the trans isomers (the active ones) of camfentamine, nortilidine & what I was suggesting. Tilidine is a prodrug, N-demethylation yields nortilidine which is about as potent as morphine.

It's interesting that their are a few opioids in which the secondary amine is the active and at least one (dezocine) in which the primary amine is the active.
But on the Wiki page of tilidine, I included a link to the patent for isotilidine which does not have an (ethyl) ester of a carboxylic acid but rather the propanoate ester of a tertiary hydroxyl moiety. You may recall that MPPP is often referred to as being the 'reverse ester' of pethidine.
 
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