What structual features contribute to an opiates subjective effects?

[thesomoan]

I have recently been doing a lot of research into opiates. I understand the concept of lipophilicity and rate of action (the faster the rate of action the greater the subjective rush), however I do not completely understand what determines mu agonism and the subjective euphoria, to make matters more complicated as far as I can tell greater mu agonism does not necassarily mean greater euphoria. I have compared the structures of three common opiates: methadone (long duration, high mu agonism, low euphoria) morphine (moderate duration, mu agonism, and high euphoria), and fentanyl (short duration, ridiculous mu agonism, and moderate-high euphoria)

methadone:

morphine:

fentanyl:

Now the primary similarity as far as structure they all appear to be trigonal to some extent and all have three hexane rings with various intermediates. They also all had similiar features which they share with most organic molecules like the presence of OH etc.

My question is what physical features on an opiate molecule contribute to each of those three characteristics?

 

[23536]

thread that's a bit related (though fentanyl doesn't comply)

I'm pretty sure most in here know the morphine rule, but here's a reminder:
- has tertiary amine
- has quarternary carbon
- aromatic ring connected to quart. carbon
- 2 carbon chain between tert. amine & quart. carbon

[example:]

methadone to me is quite euphoric (much much better than oral hydrocodone let's say)

 

[thesomoan]

Thank you I am actually kind of "self teaching" myself about all these things so I was completely unaware of the morphine rule. However that gives an idea of whether or not a molecule will have opiate effects but doesn't really give an indication of what the subjective effects will be. I found an article which is essentially looking at the reverse of my question
http://www.aapsj.org/view.asp?art=aapsj070243
but additional information would be really appreciated.

 

[lolwhatzdrugs]

thread that's a bit related (though fentanyl doesn't comply)



methadone to me is quite euphoric (much much better than oral hydrocodone let's say)

What I was going to say, not only is methadone euphoric, but it lasts, and lasts, and lasts.

I can see morphine being more euphoric (from personal experience), I mean hell, heroin is a prodrug of morphine.

 

[23536]

I found an article which is essentially looking at the reverse of my question

efficacy at MOR isn't entirely predictive of enjoyability.

---

Is it possible to measure enjoyability in animal studies? I know they measure self-administration with morphine levers and similar devices, but is there any way to measure emotional effects?

The question is not trivial: an ideal antidepressant would reliably make the patient feel great. Whichever company markets such a psychiatric drug would become a superpower.

 

[lolwhatzdrugs]

The question is not trivial: an ideal antidepressant would reliably make the patient feel great. Whichever company markets such a psychiatric drug would become a superpower.
[/hr]

It's called soma (not muscle relaxant) but no one knows what it contained (actively).