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Theoretically longest lasting drug (some super agonists or?)

BadBoy377 said:
So what happens physiologically as a result of a dose of oxymorphazone or chloroxymorphamine? The receptors are all permanently blocked and does this cause death in the subject or some kind of severe dysfunction?
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If drug is irreversible it isn’t a problem, it can be in fact less toxic than some reversible counterpart.

What I assume would cause real problems is if irreversible compound both binds to receptors with higher affinity (and is being non-competitive) than endogenous molecules targeting same receptor(s) and manages to bind to significant % of same receptors.

I think for that scenario to not be lethal or severely damaging many things would need to be tweaked in a very specific way but it’s still possible that depending on what receptors and how exactly some substance is functioning such real and relatively safe compound could be made. I don’t think that it’s likely that well balanced irreversible super agonist for lets say melatonin receptors would necessary kill or really damage person but I might be wrong.
 
The problem is that the body treats the receptor as being 'poisoned' so it's internalized and mitosis occurs.

Monoamines oxidase is a class of enzymes so the body fully expects them to bind with something and be removed.

So while irreversible ligands don't automatically pose the same risks as, say, potent agonists, they are seriously messing with the homeostasis of the body. If you read the references on such compounds, you tend to find that serious issues turn up. Maybe it can be solved and maybe not but it's simply not an area of research that has been used other than to specifically poison receptors i.e. chemotherapy.

The thing about science is that for every fact we learn, it reveals (on average) 3 or 4 things we didn't even know we didn't know...
That is why the Dunning-Kruger graph never rises to the initial level of 'oh, this is simple' and why the more qualified a person is, the more careful they are in replying to a specific question... because they know that 'best evidence' is merely the weighting of a probability. We will never know a single thing for 100% certain.
 
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