Mu Opioid Receptor Subtype Characterization

[LuxEtVeritas]

Anyone know of papers dealing with this in respect to the distinct pathways and/or effects each affects (Mu 1,2 and 3)

Naloxazine can specifically antagonize Mu1 so it would at least show what 'drops out' when that is fully antagonized

TIA

 

[MurphyClox]

This answer deals not exactly with your question, but hopefully it helps a bit anyway:

Subtypes of µ (µ1, µ2), δ (δ1, δ2) and κ (κ1, κ2, κ3) receptor have been proposed based primarily on binding studies with poorly selective ligands or in vivo studies. Only three naloxone-sensitive opioid receptors have been cloned, and while the µ-receptor in particular may be subject to extensive alternative splicing, this has not been functionally correlated with any of the proposed subtypes. Thus, there is at present no molecular basis for any of the opioid receptor subtypes, although it remains possible that they are formed by hetero-dimerization of opioid receptors with each other
or with other 7TM receptors

Adapted from:
Alexander, Mathie & Peters
"Guide to Receptors and Channels (GRAC), 3rd ed."
Br J Pharmacol 2008, 153(Suppl. 2), S1–S209

and originally published in:
Jordan & Devi
Nature 1999, 399, pp.697–700

Peace! Murphy

 

[LuxEtVeritas]

selective ligands are scarce but Naloxazine is a specific antagonist and thus holds some keys i think if research were tailored corrects

anyway, i guess some conjectures i have on Mu opioids and their effects and how it relates to subtype potency variance and such will not be tested anytime soon

 

[Ham-milton]

was it not found that propoxyphene was mu2 selective?

 

[LuxEtVeritas]

i see your old post now here quoted below and if accurate is interesting and enlightening

This is what i thought as Mu2 has very mild analgesic tendencies (more simply dulling), is the site responsible for respiratory depression, sedation, and the body load feel...basically fully depressive, likely activating predominantly barbituate type paths, as well as depressing smooth muscle so the constipation side effect is found here as well...mostly non-desirable stuff,...

notably the 'newer' natural opioids such as Mytragynol (this should become the accepted term for 7-hydroxymitragynine, much more elegant ) appear to have greater preference for Mu1 and thus lack a bit of the body load and sedation some desire but have the euphoria and analgesia and lesser side effects for a better therapeutic index

i have seen this as well in another natural opioid some have just been the first to research %)


You really CAN'T get "HIGH" on Propoxyphene. There are a few subtypes of the mu receptors, but for this let's stick to mu1 and mu2.


Mu1 is responsible for euphoria and analgesia. This is what has made it impossible to find a mu-opiate receptor agonist (MORA) that doesn't cause addiction. Some drugs are extremely Mu1 selective. Fentanyl is one, as is 6-MAM as I recall.

Mu2 is responsible for sedation and respiratory depression. It does not apparently contribute in any significant way to either euphoria or analgesia. Propoxyphene is a highly Mu2 selective. It does no produce any significant analgesia- it's actually been found to be weaker than a standard dose of aspirin.

Unfortunately for everyone who abuses it, while tolerance rises to the sedation it produces, it does not rise to the respiratory depression. This is a major drawback of Propoxyphene abuse. Overdose-levels never really increase even after years of frequent use. What would kill a neophyte is not much less than what would kill a 150mg-daily heroin addict.

Another, much more dangerous aspect: There is an extremely short time from ingestion to death. There are many cases of death occuring within 5 minutes of ingestion. Unfortunately Medics don't have the power that kid does in "Jumper"

 

[Ham-milton]

I actually have that saved on my computer to post every time someone asks "Is Darvon any good?"

 

[Mr Blonde]

^ May I please do the same, giving due credit?

 

[immad]

I was under the impression that fentanyl caused more respiratory depression than morphine and the like (wiki says it too). Since your reasoning looks sound, I guess I'm wrong?

 

[nuke]

Propoxyphene gets me high, or at least, heavily sedated and mildly euphoric, I can't tell much of a difference between it and hydrocodone to be honest, but I never get opioid euphoria. Maybe I'm some kind of freak born with shitty Mu1 receptors.

 

[LuxEtVeritas]

^ it is likely mostly the sedation and body load you feel as it has i believe marginal euphoria, though indeed if you have some Mu1 genetic variant it may compensate a bit

 

[Hammilton]

I was under the impression that fentanyl caused more respiratory depression than morphine and the like (wiki says it too). Since your reasoning looks sound, I guess I'm wrong?

Wrong- fentanyls are some of the safest drugs there are. On the whole, they produce far less respiratory depression (on a dose-equalized basis).

@Muphy-

Feel free. It comes up all the time, and having to have this new name, no one will accept what I say as pure genius unless you're quoting it (please quote with my new name though! I gotta build up street cred!)

 

[QuasiStoned]

Wow, so that's why I found kratom to be euphoric, but found it to have very little body load. That's very interesting... I want to order more kratom now.

 

[MurphyClox]

@Murphy:
Feel free. It comes up all the time, and having to have this new name, no one will accept what I say as pure genius unless you're quoting it (please quote with my new name though! I gotta build up street cred!)

Will do so, pal. No prob!

 

[MattPsy]

Like nuke, propoxyphene gets me high... not that it's a very high quality high, less pleasurable than codeine, but still a decent high. I'm not some kid who catches a buzz from railing an acetaminophen tablet, either.
Unlike nuke though I definitely do experience opioid euphoria, and I notice a LOT of difference between propoxyphene and hydrocodone.

 

[LuxEtVeritas]

i assume propoxyphene is not totally selective, just skews harder to the Mu2 thus it will engender Mu1 effects at high enough doses

that is my guess

or Mu2 may have some overlapping effects in the DAergic/euphoric/analgesic area, but are far less pronounced