So how does the binding of an agonist to a receptor work

Factual Questions
1

You’d assume I would know this, but I don’t.

I know binding energy is a measure of how strongly the agonist binds to the receptor. But what does that mean in practice? What does agonist A with more binding energy than agonist B mean? Does agonist A just displace all the agonist B molecules attached to the receptors? I assume this also applies to antagonists. I know that hallucinogens like LSD or mushrooms work because a molecule in them is an agonist to the 5HT2A serotonin receptor. But the antidepressant trazadone is an antagonist to the 5HT2A serotonin receptor. So if someone wants to end a bad trip, they take trazadone and I assume the trazadone replaces all the LSD molecules from the 5HT2A receptors.

How does it actively displace it? Wouldn’t the agonist have to constantly be attaching and detaching for a stronger affinity agonist to come along and displace it, or can the stronger agonist somehow remove the weaker agonist from the receptor by bumping into it and taking its place?

So how does one agonist have a stronger effect on the receptor vs another agonist? Like does one agonist result in a stronger biochemical effect, or is the effect the same irrelevant of the agonist, is it like a on/off switch or is there more of a continuum of effects?

Why do doses of the same drugs in the same class vary so differently? Why is fentanyl 100x more potent than morphine despite having a similar MW? Because the MW are about the same, it means the moles of molecule you get in a 10mg dosage are the same. But why does one drug cause so many more effects when the number of molecules in a 10mg dose is about the same at about ~10^18 molecules in a 10mg dose?

Aren’t all the drugs just activating the receptor, which triggers a cascade of cellular reactions? Why does one agonist have 100x more potency than another agonist of the same receptor?

For that matter, how do antagonists have different effects? PCP is an NMDA receptor antagonist that produces symptoms at 5mg, but DXM is also an NMDA receptor antagonist that produces similar symptoms at doses closer to 400mg. So why the difference if you’re just blocking a receptor?

And what is an inverse agonist? Is it an antagonist that actively blocks downstream cellular effects when other agonists attach to other receptors on the same cell?

Whats the difference between a reversible and irreversible agonist? is the irreversible one covalently bonded to the receptor while the reversible one is bonded by ionic or van der waals forces?

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Mechanisms such as enzymes breaking up the neurotransmitters or drugs, reuptake of the presynaptic neuron to “reuse” etc.

Lots of ways, including multiple types of receptors - the classic example is acetylcholine and drugs that affect the system can hit two main classes of receptors: nicotinic or muscarinic. Drugs like nictotine affect the first much more than the latter, while muscarine (from certain mushrooms) affect the latter more.

You mention NMDA below, those receptors are one of the 3 main ones that operate on glutamate.

In nature drug-receptor interactions aren’t always a clean 1:1 relationship.

I’m not familiar with fentanyl specifically but the effect appears to be that it has a greater binding affilnity, by being able to form better ligands.

[quote=“Wesley_Clark, post:1, topic:1007443”]
And what is an inverse agonist? Is it an antagonist that actively blocks downstream cellular effects when other agonists attach to other receptors on the same cell?[/quote]
An inverse agonist provides an “opposite” effect vs. just blocking the effect.