Opiates-- Morphone vs. Codone suffix: What's the difference?

[enak]

Hi all,

I've been wondering for a while now about the differences between morphone and codone drugs (hydrocodone vs. hydromorphone, oxycodone vs. oxymorphone for example)

What sets these two supposedly different drugs apart?

I see that often people claim to get a better high on "-morphone" drugs. Why is this?

When would "-morphone" drugs be used instead of "-codone" from a medical standpoint? (During surgery, certain cases, etc.. I have no intention of trying to get either of these types of drugs, simply curious.)

Thanks for the help.

 

[LucidSDreamr]

The morphones and codones differ from each other by the presence of the boxed hydroxyl group in morphones vs the methoxy group at the same location in codones.

Most codones are metabolized into the morphone by removal of the CH3 group at this location. This metabolism produces a stronger drug.

morphones are generally stronger than their codone counter parts.

 

[sekio]

The unmasking of the pehnolic OH allows for greatly increased interaction with the mu-opioid receptor.

Codeine itself actually has next to no activity as an opioid painkiller if it isn't metabolized to morphine, compared to its "isomer", heterocodeine (6-O-methylmorphine). The affinity for mu-OR can be boosted by conversion into hydrocodone, oxycodone, etc.

However, the unmasked phenol also sort of ruins the pharmacokinetics of the drug by greatly increasing polarity, hydrophilicity, and hence metbaolism/excretion/low BA. Compare the oral BA of codeine/oxycodone/hydrocodone (80%+ BA) to morphine, hydromorphone, oxymorphone etc (10-30% BA). Often the 3-O-methyl opioids are "prefered" because they have much more oral BA and hence are less likely to be abused by snorting or IV use.

 

[Hodor]

"-morphone" type drugs are generally much more powerful than their -codone counterparts, but their oral bioavailability (i.e. how much of the drug actually gets into the bloodstream if you eat rather than shoot it) is fairly low, whereas -codones generally have a fairly good oral BA. This is because anything you take orally first has to make it through the liver ("first pass effect"), which is trying to eliminate potential toxins, and having that hydroxyl group capped with a methyl makes it much harder for your body to immediately dump your precious opioids into your urine - at the cost of also making the drug worse at binding to the receptor.

Oxycodone, for example, is technically *weaker* than morphine, but its superior oral bioavailability means than mg for mg, OxyContin is stronger than MS Contin. IV'd, on the other hand, morphine is significantly stronger.
Oxymorphone is technically ten times as powerful as powerful as morphine, but since even morphine's poor oral BA (~30% ) is still better than oxymorphone's atrocious oral BA (~10% ), Opana is "only" ~3 times as strong as oral IR morphine.

Edit: Sekio beat me to it

 

[enak]

Thanks for all the help guys, I have a much better understanding now.

Have a great day.

 

[Hodor]

Thanks for all the help guys, I have a much better understanding now.

Another thing you might find interesting: The difference between "Hydro-" and "Oxy-" is that the oxy-version has an extra hydroxyl group at the 14-position. This makes the "oxy-" version more powerful, but also decreases its bioavailability. IV oxymorphone is significantly stronger than IV hydromorphone, but since oxymorphone's oral BA is so abysmal, oral hydromorphone is slightly stronger than oral oxymorphone (hydromorphone's oral BA is better than morphine's, so around 3 times that of oxymorphone).

Oxycodone, on the other hand, has a pretty decent oral bioavailability, so even though hydrocodone's oral BA is likely larger, the relative difference just isn't big enough to compensate for oxycodone's significantly greater potency, meaning that oxy is the stronger drug, both orally and when iv'd.