Neuropharmacology of opiates vs opioids

[Frozenaddict]

Hi everyone! I just registered for bluelight after many months of frequently finding well written articles here - keep up the good work. I'd like to throw out a question I've had in the back of my mind for a while now. As many of you may have experienced, there are apparent differences in the experienced effects of natural opiates as compared to their partially or fully synthetic counterparts. My question is, what is the pharmacological basis of these differences? If both types of drugs are hitting the same types of receptors, what is the basis of their differences? Could this have to do with the polarity of the molecules themselves as they relate to the polarity of receptors? Is there a more diversified spectrum of receptor types than we currently know about? Discuss

 

[nAON]

From what I thought it was a fairly arbitrary naming convention - opioid referring to anything that hits an opi receptor, and opiate to drugs that were derived from chems found in opium (or might be the other way round, can't quite remember ). Dunno if there's any way to differentiate them through binding profiles etc.

 

[serotonin2A]

I don't think it is correct to attribute these differences to opiates vs. opioids. Some opiates are associated with some of the effects you are describing.

The different effects are caused by:

1) Differences in binding to mu subtypes. Mu is generally thought to mediate euphoria, analgesia, and respiratory depression. There may be mu subtypes produced by alternative splicing, and some compounds may be selective for only one subtype. I've heard of mu-1, mu-2, and even mu-3 sites. There is also evidence for a mu subtype that binds the morphine metabolite morphine-6-gluconuride but does not bind morphine.

2) Selectivity for different opiate receptors. There are mu, delta, and kappa receptors. Opiates tend to bind to all three with preference to mu, but selectivity can vary widely from compound to compound. Opioids are often much more selective for one of the receptors. Fentanyl, for example, tends to selectively activate mu. The three receptors produce different subjective effects and so ligand selectivity can markedly alter the profile of effects.

3) Off-target effects. Opioids and opiates can produce effects by blocking NMDA receptors (methadone, levorphanol), the dopamine transporter (meperidine, tilidine, levorphanol), the setotonin transporter (meperidine?), and glycine receptors (thebaine).

4) Effects of metabolites. Some opioids yield metabolites that have different actions than the parent drug. Normeperidine produces convulsions and is not an analgesic.

Opioid receptors can also form dimers and it is possible that ligands that bind to the dimers preferentially may have different effects than ligands that bind to the protomers (individual receptors).

 

[endotropic]

I don't think it is correct to describe these differences to opiates vs. opioids. Some opiates are associated with some of the effects you are describing.

The different effects are caused by:

1) Differences in binding to mu subtypes. Mu is generally thought to mediate euphoria, analgesia, and respiratory depression. There may be mu subtypes produced by alternative splicing, and some compounds may be selective for only one subtype. I've heard of mu-1, mu-2, and even mu-3 sites. There is also evidence for a mu subtype that binds the morphine metabolite morphine-6-gluconuride but does not bind morphine.

The evidence for mu splice variants producing different pharmacological effects is particularly questionable in my opinion. I think points 2-4 explain most of the differences.

 

[sekio]

there are apparent differences in the experienced effects of natural opiates as compared to their partially or fully synthetic counterparts.

The weird thing is that even "partially synthetic" opioids occur naturally at low levels (hydromorphone, hydrocodone) in the poppy plant. Even oxycodone has actually been detected in nature - in certain species of orchids.

So differentiating "semi synthetic" from "natural" opioids really is incorrect; they're all just phenanthrene opioids in the end, with different properties & effects.