In-Depth Look At How Buprenorphine Works To Block Opiates

Opiates/Opioids are substances that interact with opioid receptors in the body.  The type of interaction at the receptor site depends on whether it is an Agonist or Antagonist. It is vital to understand some terms and lay groundwork to fully understand buprenorphine and how it works.

The Opioid Agonist will bind to the receptor and trigger activity.
The Opioid Antagonist will bind to the receptor as well but do not trigger activity (essentially     blocking receptors from agonist's triggering activity)

Most agonist opioids are full agonist opioids, although there are some which are partial agonist opioids.

Full Agonist will bind to and fully activate the receptor
Partial Agonist will bind to and partially activate the receptor

Buprenorphine is one of those Partial Agonist Opioids.

That is not all there is to the concept though.

Each opioid substance (agonists or antagonists) have several unique variables that define how they interact with the receptor.  Those important to understand are defined below -


Intrinsic activity - the substance's measure of activity on the receptor

Affinity - the substance's measure of binding strength to the receptor

Dissociation - the substance's measure of the separation from receptor

In other words -

Intrinsic activity is how much effect (if any) the substance will produce
Affinity is how much of a grip the substance has on the receptor
Dissociation is how long before the substance becomes separated from receptor



Buprenorphine is used in treatment of opioid dependence and addiction because of some of it's unique characteristics.  Now that we understand the opioid receptor concepts, the reason for the unique characteristics of buprenorphine will be easier to grasp.

Below are 3 diagrams that illustrate the opioid receptor concepts and how they relate to buprenorphine's unique characteristics

Empty Opioid Receptor

Illustrates empty opioid receptor 

Opioid Receptor Interacting With Full Agonist Opioid 

This illustrates a unique full agonist opioid interacting with the opioid receptor

Intrinsic activity - The intrinsic activity is represented by the opioid shape and receptor pathways - 

Intrinsic activity is maximum - Opioid shape matches receptor shape perfectly therefore all pathways are activated 

Affinity - The affinity is represented by the zig zag shape around the opioid receptor -

Affinity is low/normal - zig zag around receptor is thin and reaches shallow

Dissociation - The dissociate is represented by the arrows pointing away from top of opioid shape-

Dissociation is high - arrows pointing from opioid shape are thick and extend far 

Opioid Receptor Interacting With Buprenorphine - Partial Agonist Opioid

This illustrates the unique partial agonist opioid buprenorphine interacting with the receptor

Intrinsic activity - The intrinsic activity is represented by the opioid shape and receptor pathways - 

Intrinsic activity is low - Opioid shape matches receptor shape only partially (on the bottom) therefore some of the pathways are activated 

Affinity - The affinity is represented by the zig zag shape around the opioid receptor -

Affinity is high - zig zag around receptor is thick and reaches deep

Dissociation - The dissociation is represented by the arrows pointing away from top of opioid shape-

Dissociation is low - arrows pointing from opioid shape are thin and do not extend far 

The unique full agonist opioid in purple is representative of most common full agonist opioids (morphine, hydrocodone, oxycodone, etc.) when compared to buprenorphine.  Here is why-

• The intrinsic activity is much higher than buprenorphine 
• The affinity is much lower than buprenorphine 
• The dissociation is higher than buprenorphine

Using only a full agonist opioid similar to the one represented in the diagram means 

• It will bind to receptors because it is the only opioid present
• It's full activity will produce great analgesic effects in user
• It's high dissociation allows the binding and full activity for a short time period (therefore, to achieve consistent activity on the receptor - requires multiple administrations daily)

IN CONCLUSION

Using Buprenorphine within hours of any full opiate agonist will cause the receptors to immediately replace the full agonist with the buprenorphine.  In an opioid dependent person, this often results in precipitated withdrawal symptoms because their body is accustomed to the full opioid activity of a full agonist.  

Buprenorphine works to "block" other opioid use because it clings very strongly to the receptor, and remains there for a very long time.  Any other opioid introduced into the system cannot replace the buprenorphine at the receptor site, and is therefore effectively useless.