Irreversible Agonists??

[DeathIndustrial88]

This might be the wrong place to post this, so feel free to move or remove it.


I've always heard of "irreversible agonists" but today it popped back into my mind.
Apparently they're agonists that never stop activating the receptor. Or maybe they do but they never become unbound from it. I forget which.

There are also irreversible opioid agonists out there. So does this mean it would be activating your receptors....forever?
What would happen if your opioid receptors were being activated permanently? Wouldn't it kill a person eventually?

Can irreversible agonists not be anatagonized then?

Apparently Oxymorphazone "is only around half the potency of oxymorphone, with higher doses the analgesic effect becomes extremely long lasting, with a duration of up to 48 hours". Why would it wear off after 48hrs if it's bound & irreversible? If it never leaves the receptor, then what exactly happens? Does this mean you'd have oxymorphazone stuck in your body forever? I'm very confused on how irreversible agonists would work, wear off or not kill anyone. Or what they would even be useful for.

Any other fun facts or info about irreversible agonists that anyone has to add?

 

[polymath]

If you activate a receptor irreversibly with that kind of agonist, the neurons will notice that and will destroy (internalize) the receptor in 2-3 days. Then they will grow new receptors to replace the irreversibly bound ones. So an irreversible opioid agonist causes an effect that lasts for a couple of days or a bit more than that. Naloxone will not stop the intoxication caused by an irreversible mu opioid.

 

[DeathIndustrial88]

If you activate a receptor irreversibly with that kind of agonist, the neurons will notice that and will destroy (internalize) the receptor in 2-3 days. Then they will grow new receptors to replace the irreversibly bound ones. So an irreversible opioid agonist causes an effect that lasts for a couple of days or a bit more than that. Naloxone will not stop the intoxication caused by an irreversible my opioid.

Hey, thanks for the info!
Makes much more sense!

 

[Joey]

If you activate a receptor irreversibly with that kind of agonist, the neurons will notice that and will destroy (internalize) the receptor in 2-3 days. Then they will grow new receptors to replace the irreversibly bound ones. So an irreversible opioid agonist causes an effect that lasts for a couple of days or a bit more than that. Naloxone will not stop the intoxication caused by an irreversible mu opioid.

Is the same true for naloxone? This sounds extremely dangerous.

 

[TheUltimateFixx]

Is the same true for naloxone? This sounds extremely dangerous.

?? Naloxone is a full ANTAGONIST. It blocks any opiate from binding to opiate receptors and it only lasts for about an hour, which is why somebody on a heavy overdose is going to need repeated doses of naloxone as the opiates stay in your system longer than the antidote.

 

[bingey]

?? Naloxone is a full ANTAGONIST. It blocks any opiate from binding to opiate receptors and it only lasts for about an hour, which is why somebody on a heavy overdose is going to need repeated doses of naloxone as the opiates stay in your system longer than the antidote.

Apparently it doesn't block these irreversible agonists effectively

 

[Fertile]

I think the term people should use is 'irreversible ligand'. Usually they form a co-valent bond with the site. Some crude cancer medicines work by irreversibly binding with certain cellular machinery and kill ALL cells, but cancer cells much more effectively because they are growing faster. That's where fractination comes in.