exotic opioids (pics)

[wungchow]

bremazocine (k-opioid receptor ligand)

eptazocine (k-agonist mu-antagonist with analgesic properties)

dezocine

trefentanil

brifentanil

pentamorphone

phenomorphan

 

[Tehuti]

Love the thred, got any more?

 

[haribo1]

I would think that phenomorphan would be a pretty strong mu agonist. Dezocine is already in use in surgery, but isn't widely accepted. I'm surprised that the 7-8 double-bond in pentomorphan hasn't been reduced, sure thats not an error (a 6 ketone without the 7-8 reduced is less potent than a 6-OH)

 

[Jabberwocky]

whats the need to create new opiods (question mark). To get around patents (question mark).8)

 

[adder]

I'm surprised that the 7-8 double-bond in pentomorphan hasn't been reduced, sure thats not an error (a 6 ketone without the 7-8 reduced is less potent than a 6-OH)

The stuff is pretty strong itself but then who would fuck around with a 6-keto for no reason.

 

[Jamshyd]

I'm glad that only two of those are fentanyls

eptazocine sounds like a torture instrument. I don't even want to know what the military does (did?) when it synthed it.

 

[Tehuti]

haribo1 does that bri fent fall under the uk catch all law?

 

[vecktor]

haribo1 does that bri fent fall under the uk catch all law?

no by virtue of the aryl substitution in the piperidine ring ony alkyl and alkenyl are proscribed.

 

[Tehuti]

excellent smithers,, evil laugh

 

[haribo1]

no by virtue of the aryl substitution in the piperidine ring ony alkyl and alkenyl are proscribed.

Yes, but only when there is an ester or reversed ester in the system. Like I said, they missed the ketone, so bemidones would fall outside the act (apart from ketobemidone which is specifically stated).

 

[jdfc]

Has anyone seen any fentanyl SAR that has led to analogs of extreme potency (100x M or greater) that also have changes to the neuropharmacology of the parent molecule?

By this I mean any fentanyl derivatives with activity other than 5-HT1A and Mu agonist properties?? Or has SAR data shown that all fent derivs ever made posessed similar serotonin/opioid receptor profiles?


Surely there must be a fent modifcation somewhere out there that led to dopamine reuptake inhibitory actions or kappa agonist or even just broadened its serotogenic actions...

 

[FractalStructure]

i dont think i wanna be taking any k-opioid agonists. doesnt that cause hallucinations? (i could be wrong and confused)


i just remember this one time getting some butorphanol and i think i remember it being a kappa-agonist (antagonist at mu i believe) and that shit was not fun at all and did cause hallucinations.

 

[jdfc]

i dont think i wanna be taking any k-opioid agonists. doesnt that cause hallucinations? (i could be wrong and confused)


i just remember this one time getting some butorphanol and i think i remember it being a kappa-agonist (antagonist at mu i believe) and that shit was not fun at all and did cause hallucinations.

ya was more interested in either a serotogenic-based hallucinogenic mu-agonist 4-anilidopiperidine with possible DRI or just a DRI with mu-agonist actions... in mcg range of course

I guess dihydroetorphine derivs and possibly certain benzimidazoles could also be alternative routes to the same profile if SAR has ever shown a way to knock DHE or etonitazenes profile to a less selective state yet retain their in vivo potency.

 

[jdfc]

and also, Salvinorin A is probably the most common kappa-agonist!

 

[vecktor]

ya was more interested in either a serotogenic-based hallucinogenic mu-agonist 4-anilidopiperidine with possible DRI or just a DRI with mu-agonist actions... in mcg range of course

I guess dihydroetorphine derivs and possibly certain benzimidazoles could also be alternative routes to the same profile if SAR has ever shown a way to knock DHE or etonitazenes profile to a less selective state yet retain their in vivo potency.

unfortunately the reason that etorphin or etonitazene or <insert dangerous opioid here> have such high potency is that they are optimal for binding to the opioid receptor, which of course is a different shape to the DAT site or whatever. so in order to be optimal to bind to dat and to the say mu opioid receptor then both receptor sites would have to be the same shape, and we already know they aren't.
so as a general rule selectivity and high potency tend to go hand in hand unless there are several very closely related sites. for example the 5ht2a and 2c site are almost identical from an agonist point of view,though the bulkier antagonists can discriminate.

 

[Jabberwocky]

^ 1-methyl-psilocin is a selective agonist at 5HT2C and does nearly nothing at 5HT2A.

 

[butane]

I'm all for exploring new compounds and whatnot, but where do you cross the line of practicality? Why go through so much work when such a damn fine opiate as diacetylmorphine can be easily procured through known methods?

 

[vecktor]

I'm all for exploring new compounds and whatnot, but where do you cross the line of practicality? Why go through so much work when such a damn fine opiate as diacetylmorphine can be easily procured through known methods?

the main reason is legality,
diamorphine = jail

 

[mad_scientist]

unfortunately the reason that etorphin or etonitazene or <insert dangerous opioid here> have such high potency is that they are optimal for binding to the opioid receptor, which of course is a different shape to the DAT site or whatever. so in order to be optimal to bind to dat and to the say mu opioid receptor then both receptor sites would have to be the same shape, and we already know they aren't.
so as a general rule selectivity and high potency tend to go hand in hand unless there are several very closely related sites. for example the 5ht2a and 2c site are almost identical from an agonist point of view,though the bulkier antagonists can discriminate.

There are several compounds which are both mu-opioid agonists and dopamine reuptake inhibitors, lefetamine and meperidine are the best examples. However both of these compounds are fairly low potency, because like vecktor says in order to get decent binding to multiple targets with different shapes, there will always be a loss of selectivity.

Meperidine looks like a promising lead compound as there are derivatives which appear to be both stronger mu agonists and stronger DAT inhibitors than the parent compound, plus synthetically plausible.

As for compounds that combine serotonergic hallucinogen 5HT2A agonist properties with mu-agonist, this seems less likely. Ibogaine shows both of these effects (as well as being a DAT inhibitor also!), but this is largely because its a terribly promiscuous and "dirty" compound with very low potency, dose in the high hundreds of milligrams so its little surprise that it binds to many different targets.

Optimising ibogaine to improve both 5HT2A and mu-opioid affinity seems unlikely as the pharmacophores are so different, at least there are some mu-agonists that are a similar shape to some DAT inhibitors, so crossover is possible, but none of the 5HT2A agonist hallucinogens look anything like any of the mu agonists. And ibogaine is a hideously complex and difficult structure to play around with to try and make new analogues!

 

[butane]

the main reason is legality,
diamorphine = jail

I can definitely see the rationale behind that, if one is not in the US. Sadly, here in the states, I'm certain it would make no difference. Like any cop who finds you all smacked out with a needle, spoon and tie along with some fine white powder in a bindle is going to let you go because you tell him, "it's not heroin, it's xxx new opioid!"

However, if you ever come up with something that rivals or surpasses heroin in its subjective experience, count me in!!! I'd love to get my hands on some diacetyloxymorphone....