any possibility of a 'super-narcan'?

[(zonk)]

Now that super powerful opiates are circulating like crazy. It seems some like w-18, u-47.., and carfentanil are not only dangerous in terms of potency but if not more so that they are very resistant to naloxone in some cases. Would it be possible to make a more powerfull carfentanil or methadone based mu opiate antagonist? If it were possible I think there'd be a good market for this now to say the least.

Any thoughts on structure?

My apologies if this has been discussed already.

 

[kleinerkiffer]

What about Diprenorphine?

 

[Nagelfar]

What about Diprenorphine?

Yes, Revivon (Diprenorphine) was made in-case etorphine was spilled on the workers tranquilizing the elephants, this was thought of long ago, there are many such substances, and they are inverse agonists; I wonder how their extreme reverse agonism (instead of simple neutral antagonism) would be noticeable to those naive to opioid dependence (as Naloxone & Naltrexone putatively are)

Xorphanol, Stadol/Butorphanol etc. there are many such super-potent opioid 'inveragonists'

 

[kleinerkiffer]

^ from Wikipedia

Because diprenorphine is a weak partial agonist of the opioid receptors rather than a silent antagonist, it can produce some opioid effects in the absence of other opioids at sufficient doses.Moreover, due to partial agonism of the KOR, where it appears to possess significantly greater intrinsic activity relative to the MOR, diprenorphine can produce sedation as well as, in humans, hallucinations.

 

[Nagelfar]

weak partial agonist, which is overwhelmed by the super strong inverse agonist, not a neutral/silent antagonist

 

[adder]

Xorphanol, Stadol/Butorphanol etc. there are many such super-potent opioid 'inveragonists'

These are not inverse agonists either. Where do you get this information from?

weak partial agonist, which is overwhelmed by the super strong inverse agonist, not a neutral/silent antagonist

What?

 

[Nagelfar]

These are not inverse agonists either. Where do you get this information from?

I suppose I wasn't understanding the agonism of Revivon as (extremely?) partial but higher-affinity than super-(above-"full")-agonism without being neutral, I get it now after re-reading.

What?

I was theorizing in absence of my understanding of what was being asked, but I see it now; AFAIK one of the few neutral-agonists is 6β-Naltrexol and I wasn't considering the possibility of the affinity of a compound still being an agonist even if weakly, able to overcome the lesser affinity of another very strong agonist substance without matching it in strength of affinity, but 6β-Nal isn't that. So is this less rare than neutral agonism among phenathrene opioids? What others like Revivon are there? And of course, the OP's question now likewise piques my own interest seeing my assumptions on the matter differently.

So I learned that it is possible that Revivon can be abused just as a regular agonist in some respect. Imodium and now Immobilon's antidote too. Don't give me any ideas guys, what are you thinking. ;-j

I am loving the Bentley like morphinans more and more, the more I learn and the more about what they really do sinks in.

 

[RedRum OG]

Narcan is dose dependent up to pretty goddamn high. Inverse agonists are relatively unknown/not researched as their marketable effects are very few. I think they hold some potential.

 

[Nagelfar]

Narcan is dose dependent up to pretty goddamn high. Inverse agonists are relatively unknown/not researched as their marketable effects are very few. I think they hold some potential.

Low-dose naltrexone therapy is a viable, non-narcotic overdose antidote, use for inverse agonists of a very specific affinity range.

 

[belligerent drunk]

Have any antagonists/weak partial agonists of the fentanyl structure been explored? Following the same motif of adding an allyl/cyclopropylmethyl group to the nitrogen instead of methyl in morphinan-type opioids to make them have antagonistic properties instead of agonistic.

 

[serotonin2A]

Have any antagonists/weak partial agonists of the fentanyl structure been explored? Following the same motif of adding an allyl/cyclopropylmethyl group to the nitrogen instead of methyl in morphinan-type opioids to make them have antagonistic properties instead of agonistic.

Replacing the N-phenethyl group in the fentanyl class with an allyl group produces a marked reduction in potency, but doesn't seem to reduce efficacy (at least not low enough to abolish their ability to act as analgesics).