Great read, opioid chemistry and pharmacology is so underappreciated, I really wish there was a book like PiHKAL but for opioidsThere are a few structural characteristics which define whether a morphinian is going to be (significantly) active by itself or not. in the case of oxycodone it's due to having a carbonyl group at C6 + a simple (saturated) bond between C7-C8 + a hydroxy group at C14 (codeine has neither of those things). All of which seem to increase activity in a very big way.
So a "blocked" hydroxy group (phenol) at carbon n°3 doesn't automatically kill the activity, it just decreases it. But it does have a pretty big advantage as well: it usually makes the drug more orally bioavailable.
This may be one of the reasons why doctors tend to prefer codeine, hydrocodone and oxycodone over morphine, hydromorphone and oxymorphone (but it's mostly due to the fact that they're perceived as being less "abusable").
In the case of heroin, the acetyl group does "block" the phenol as well, which actually makes the drug almost completely inactive (but also more lipophilic). However, that particular ester group gets broken down very quickly upon entering the body, so heroin ends up being a very effective pro-drug for 6-monoacetylmorphine which is a potent opioid.
I made a quick summary of the main structural things that tend to modulate the opioid-like activity of those drugs. Obviously it isn't 100% complete and there are exceptions.
Green= increases activity
Red= decreases activity
No way, the whole molecule is so reactive something as "crude" as hydrogen peroxide would widely disrupt the molecule
I flipped the picture and added some info. Hope it makes it easier to read and understand when comparing it to the examples bellow.
Yeah it's complicated stuff, you go step by step (I'm definitely not an expert on opioid receptors either). But the way people figured out that oxymorphone is stronger than codeine or morphine is basically through trial and error, you modify the molecule bit by bit and test it to see what happened after each modification.
Those things allow the molecule to bind to the receptor much better than a molecule which doesn't have those characteristics.
My knowledge is very unevenly balanced. I used internet and watched Robert Sapolskys neuroscience classes that Stanford made available on YouTube. So I learned a bit about CNS, neurons, how they fire, communicate, how neurotransmitters (or other molecules) bind to receptor sites. I have really basic level of pharmacology understanding (without chemistry that is needed to really understand it, as I said). Also have some notion about agonists/partial agonists/antagonists of target site being charged in a way that they are more or less pulled/repelled by receptors, so chemistry is actually electrical/magnetical in nature. Not to make it unnecessary long - I understand some things that are more complex and yet don't have basics at the same time. That's why, just yesterday I started to read a book "Nursing pharmacology" which seems like a light, but very needed read if I'm gonna go all the way to gain more functional knowledge. I give myself 10 years as I will study on my own (don't have money for college, even though in Croatia it is much cheaper than in USA). I'll try to create some more direct way to actually understand psychopharmacology on "bachelor's level". Not to get employed in that area but cause I find it very interesting. I will need a lab for chemistry but I will make one when I get on the level where lab is actually needed. Thank you for explaining. This last post was more "on my level". 