Bupe Buprenorphine blocks epsilon receptors?

[DeathIndustrial88]

This article says buprenorphine "blocks epsilon receptors at low doses"..

Buprenorphine: A Unique Drug with Complex Pharmacology

Buprenorphine, an opioid with mixed agonist-antagonist activity at classical opioid receptors, has been approved recently for the treatment of opioid dependency. Buprenorphine is also used as an analgesic. The buprenorphine dose-response curve is sometimes ...

www.ncbi.nlm.nih.gov

This is the first time reading about this.

Anyone have any idea what actions blocking the epsilon receptor might have? Is this something people should be doing long term?

Do other opioids block this receptor?
What is it for?

I have googled but would like better layman term explanations & conversation about this in general.

What else does bupe do that is strange or unique compared to other opioids?

 

[negrogesic]

The closely related etorphine is an agonist of the yet to be confirmed (or yet to be cloned) epsilon opioid receptor. Buprenorphine is very similar in structure to the ultra potent etorphine but most notably with an added cyclopropyl group, which produces an effect similar to a key that has been copied almost exactly but with a little metal burr left on the side. It fits the key slot and opens the lock, but not as smoothly and effectively.

The clinical relevance of buprenorphine's antagonism of the suspected epsilon receptor hasnt been characterized im sure since the epsilon receptor hasn't been well characterized itself. Im guessing many existing opioid antagonists are also antagonists of the proposed epsilon receptor. There are a handful of suspected opioid receptors, epsilon, lambda, zeta, maybe more. None have been cloned as far as i know.

 

[DeathIndustrial88]

The closely related etorphine is an agonist of the yet to be confirmed (or yet to be cloned) epsilon opioid receptor. Buprenorphine is very similar in structure to the ultra potent etorphine but most notably with an added cyclopropyl group, which produces an effect similar to a key that has been copied almost exactly but with a little metal burr left on the side. It fits the key slot and opens the lock, but not as smoothly and effectively.

The clinical relevance of buprenorphine's antagonism of the suspected epsilon receptor hasnt been characterized im sure since the epsilon receptor hasn't been well characterized itself. Im guessing many existing opioid antagonists are also antagonists of the proposed epsilon receptor. There are a handful of suspected opioid receptors, epsilon, lambda, zeta, maybe more. None have been cloned as far as i know.

Wow!

I had no idea!
I wanna say I've seen or come across the epsilon receptor being mentioned before in the past, but only this time did it really make me stop and say "hmm".

That is very interesting!
This means there are still opioid receptors within us that they know nothing about how they function or interact with various opioids. That leaves a lot of room for mystery.
I wonder if they'll ever be able to clone these other receptors and study them more. It would be intriguing.

Maybe they have no clinical significance. On the other hand, I wonder if it's possible that agonism/antagonism at these receptors could affect things like our hormones or growth or in some way alter us physiologically that we do not know about, similar to how the other receptors can. I'd bet they affect the agonism at the other receptors as well possibly.

Thanks negrogesic!

 

[Skorpio]

It may be a splice varient/heteromer of the delta, kappa, or mu receptors. Epsilon agonists were not able to work in triple (delta/kappa/mu) knockout mice.

That would give a decent reason why it hasn't been cloned yet (it's not a unique gene).

The intro section to this paper is pretty good at showing the history and prior studies of the epsilon receptor (and rationale behind thinking it exists).

Sci-Hub | No evidence for G-protein-coupled epsilon receptor in the brain of triple opioid receptor knockout mouse | 10.1016/j.ejphar.2004.03.056

sci-hubtw.hkvisa.net

 

[DeathIndustrial88]

It may be a splice varient/heteromer of the delta, kappa, or mu receptors. Epsilon agonists were not able to work in triple (delta/kappa/mu) knockout mice.

That would give a decent reason why it hasn't been cloned yet (it's not a unique gene).

The intro section to this paper is pretty good at showing the history and prior studies of the epsilon receptor (and rationale behind thinking it exists).

Sci-Hub | No evidence for G-protein-coupled epsilon receptor in the brain of triple opioid receptor knockout mouse | 10.1016/j.ejphar.2004.03.056

sci-hubtw.hkvisa.net

Much appreciated Skorpio!