Receptor affinity of different opiates

[Laudaphun]

Many people out there are aware of the "blocking effect" of buprenorphine. This supposedly happens because buprenorphine while being a partial agonist, has a higher affinity for the receptors in the brain. Basically if an opiate with a weaker affinity has already binded itself to the receptor and buprenorphine is introduced it will knock that opiate off of the receptor and take its place. Or if buprenorphine is already binded to the receptor and other opiates are taken, they are not able to bind because the buprenorphine essentially blocks them from doing so.

This made me wonder about how binding affinity comes into play when the opiates in question are those other than buprenorphine. Suppose you are taking full agonists... Two chronic pain patients may be given the same time-release opiate for pain control but different breakthrough pain meds. Surely there would have to be some logic in which particular medication would be used for breakthrough pain, and I can't help but wonder how much binding affinity would come into play in such a situation. I'm no doctor or pharmacologist however binding affinity is rarely mentioned outside of when discussing buprenorphine. Surely it's possible for one full agonist to compete with other full agonists for a spot on a receptor.

It also makes me wonder about our natural endorphins and their binding affinity in comparison with different artificial opiates. Does morphine knock our natural endorphins off of the receptors? This is something that is probably a bit over my head but even so, I'm curious.

Reputation Comments on this post:

Good Topic

[Orchid_Suspiria]

Would methadone compete with buprenorphine?

[Laudaphun]

Actually I think that if someone who is a methadone patient takes buprenorphine at the incorrect time, the bupe will knock the methadone off of the receptors but since the tolerance is so high from the methadone that it will precipitate a violent withdrawl. People switching from methadone to buprenorphine are supposed to taper down to 30mg/day before attempting the switch and even then they must make sure they are well into withdrawl before taking the first dose of buprenorphine. I think the idea is to make sure that there is no methadone or very little left for the buprenorphine to knock from the receptors. Pretty much I think the buprenophines takes the place of the methadone on the receptors, but then cannot "fill the shoes" of the methadone.

I've heard people explain the blocking effect experienced by methadone patients and buprenorphine patients as being different in that the buprenorphine blocks other opiates because it physically blocks the other opiate molecules from binding, whereas a similar effect is experienced in methadone patients mostly just because the methadone skyrockets your tolerance so that you need insanely large doses of other opiates to feel them. I don't how much truth there is in that explanation but that is just the explanation given to me that has always stuck with me and made sense.

EDIT: Here I found some info that explains what happens better than I can...

A rapid and intense onset of a withdrawal syndrome initiated by a medication. In the case of Buprenorphine, because it has a higher binding strength at the opioid receptor, it competes for the receptor, “kicks off” and replaces existing opioids. If a significant amount of opioids are expelled from the receptors and replaced, the opioid physically dependent patient will feel the rapid loss of the opioid effect, initiating withdrawal symptoms. More precisely, precipitated withdrawal can occur when an antagonist (or partial agonist, such as Buprenorphine) is administered to a patient physically dependent on full agonist opioids. Due to the high affinity but low intrinsic activity of Buprenorphine at the μ-receptor, the partial agonist displaces full agonist opioids from the μ-receptors, but activates the receptor to a lesser degree than full agonists which results in a net decrease in agonist effect, thereby precipitating a withdrawal syndrome.

[Ethyl]

Originally Posted by Laudaphun

It also makes me wonder about our natural endorphins and their binding affinity in comparison with different artificial opiates. Does morphine knock our natural endorphins off of the receptors?

Yes.
A receptor is like a keyhole, it only fits one key... So.. if there are no more keyholes available (= receptors saturated), then the opiate with more binding-affinity potential (the one that sticks harder..) is the one that's going to stay in the keyhole.

You should look for binding affinity potential when comparing how different artificial opiates would react.

One more thing.. Binding affinity does not mean high effect, it may just stick to the receptor and do little..

[Laudaphun]

It's interesting that we've only just begun to understand opiod receptors and such. Even now I believe we have a limited understanding. There are three main receptors, each with different effects, and yet still there are 2 or 3 subtypes of each receptor with varying effects still. Mu, delta, and kappa being the main receptors. Each opiate has varying affinities for each particular receptor. Even beyond that, the effects are still yet to be determined by whether the drug has an agonist, partial agonist, or antagonist effect at the binding site.

Like SWIE said in the above post, the binding affinity has less to do with the effects, but rather the effects depend on the action of the molecule once bound to the receptor(whether it exhibits agonistic, antagonistic, or partial activity). I was reading today about receptors and stumbled across a chart that is pretty interesting.


S.No. 1.
µ(mu): Reduction of pain
(kappa) : Reduction of pain
(delta) : Reduction of pain

S.No.2.
µ(mu): Suppression of respiratory effort
(kappa) : Suppression of respiratory effort
(delta) : Suppression of respiratory effort

S.No.3.
µ(mu): Sensations of elation and well-being(euphoria)
(kappa) : Unpleasant sensations of anxiety or fear (dysphoria); Seeing unnatural and imaginary things (hallucinations)
(delta) : Emotional behaviour(also known technically as affective behaviour)

S.No.4.
µ(mu) : Constriction of pupils(known technically as miosis)
(kappa) : Miosis
(delta): --

S.No.5.
µ(mu): Reduced movements of the bowel(responsible for constipation)
(kappa) : --
(delta) : Reduced movements of the bowel

S.No.6.
µ(mu): Addiction (physical dependence)
(kappa) : Addiction
(delta) : --

This was originally the table I was trying to copy but formatting was all messed up so I had to type it up by hand. It was supposed to be a table showing which receptors were responsible for which activity... I'll try and put the table up in its original format so it's easier to understand.