Why do codeine and hydrocodone have the same formula but different highs?

[cowardescent]

They both have the formula C18H21NO3. I've taken codeine and hydrocodone and I can say that the latter is FAR more euphoric, long lastic, and has a shorter onset time than codeine. Codeine is good but takes long to start feeling the effects and I'd need 6-7 pills whereas with hydrocodone, I'd only need two.

The interesting this is that I felt stimulated by hydrocodone but sedated by codeine. What's the explanation for that?

 

[MsDiz]

Well yes they have the same chemical formula but they do not metabolise in the same way.

Hydrocodone is a synthetic derivative of codeine and it has a more potent metabolite hydromophone.

 

[Skorpio]

Location, location, location! Molecules are all 3 dimensional sets of atoms, and the order they are connected correlates with the effect. You could make a box or a pyramid with the same set of legos for example.

Now, why codeine is weaker, is that codeine needs to convert into morphine through the removal of a methyl group before its active. This conversion is not very efficient (although some drugs like glutethimide, cause the metabolism to skyrocket, and that combination is said to be quite fine).
Hydrocodone is active on its own, although some does convert to the stronger hydromorphone, this is not obligatory to feel high.

Somebody who is more of a medicinal chemist could go into more detail about how hydrocodones carbonyl makes it stronger and all.

 

[alarminglynefarious]

the atoms may be in the same proportions but they are bound to each other at different locations creating a different shape

 

[MsDiz]

Codeine is a pro-drug with a 200-fold weaker affinity for μ-opioid receptors than morphine. While 80% of the administered drug is inactivated by glucuronidation to codeine-6-glucuronide by uridine 5′-diphosphate glucuronosyltransferase-2B7 (UGT2B7) and N-demethylation to norcodeine by CYP3A4, 5-10% of codeine undergoes O-demethylation to morphine, its active form via CYP2D6. Without O-demethylation, codeine confers a small fraction of the analgesic potency of morphine, and much of its analgesic effect is likely contributed by a metabolite, codeine 6-glucuronide.

Hydrocodone is about 12 times more potent at the opioid receptor than codeine and about half the clearance is via CYP2D6 and CYP3A4, into an active metabolite hydromorphone, and norhydrocodone, respectively. CYP2D6 UM may have up to an eightfold greater plasma concentration of hydromorphone.

 

[Jabberwocky]

This conversion is not very efficient (although some drugs like glutethimide, cause the metabolism to skyrocket, and that combination is said to be quite fine).

Well this is interesting. I have to do some research.

Codeine is a pro-drug with a 200-fold weaker affinity for μ-opioid receptors than morphine. While 80% of the administered drug is inactivated by glucuronidation to codeine-6-glucuronide by uridine 5′-diphosphate glucuronosyltransferase-2B7 (UGT2B7) and N-demethylation to norcodeine by CYP3A4, 5-10% of codeine undergoes O-demethylation to morphine, its active form via CYP2D6. Without O-demethylation, codeine confers a small fraction of the analgesic potency of morphine, and much of its analgesic effect is likely contributed by a metabolite, codeine 6-glucuronide.

Hydrocodone is about 12 times more potent at the opioid receptor than codeine and about half the clearance is via CYP2D6 and CYP3A4, into an active metabolite hydromorphone, and norhydrocodone, respectively. CYP2D6 UM may have up to an eightfold greater plasma concentration of hydromorphone.

This is some quality information. Great job.

 

[X11400]

Location, location, location! Molecules are all 3 dimensional sets of atoms, and the order they are connected correlates with the effect. You could make a box or a pyramid with the same set of legos for example.

Now, why codeine is weaker, is that codeine needs to convert into morphine through the removal of a methyl group before its active. This conversion is not very efficient (although some drugs like glutethimide, cause the metabolism to skyrocket, and that combination is said to be quite fine).
Hydrocodone is active on its own, although some does convert to the stronger hydromorphone, this is not obligatory to feel high.

Somebody who is more of a medicinal chemist could go into more detail about how hydrocodones carbonyl makes it stronger and all.

I would add that the arrangement of these atoms in the compared molecules can have an effect on the pharmacology of the drug as well as the chemistry of the molecule.

 

[Rectify]

Hydrocodone has a ketone in the place of codeine's hydroxyl group and there is no carbon carbon double bond, so they do not have exactly the same structure. The ketone makes hydrocodone cross the blood barrier better.

 

[Nagelfar]

Yep. As so many above have said. Many different drugs, some almost wholly different, can have the same basic formula, but be utterly different in structure and therefore QSAR.

 

[MoFo_S]

Personally I think that almost all of the recreational effect from codeine comes from codeine-6-glucuronide, not morphine as people used to think. For a period of time I was taking both fluoxetine and codeine. I noticed that even if I took my fluoxetine a couple hours before the codeine, the codeine still produced its usual high. Fluoxetine is a strong substrate/inhibitor of CYP2D6, so if codeine produces its effect by CYP2D6 converting some if it into morphine, then taking fluoxetine prior should greatly reduce or eliminate its effect. But that never happened, even after I had been taking the fluoxetine for months (meaning my system should have been fully saturated by it at that point).

 

[fastandbulbous]

Just because a house uses the same number of bricks, doesn't mean they're identical buildings...