[uni_student]

Why is it that when there is Drug A (an agonist) and Drug B (an antagonist) present for a specific receptor, the antagonist binds to the receptor more preferably compared to the agonist? Thanks.

[templelane]

It is not always the case that an antagonist will bind to a receptor with a higher affinity (more preferably) than an agonist. In any set of agonist and antagonist each ligand will have its own Kd (disassociation constant). It is too much of a blanket statement to say that antagonists have a higher affinity. Look up competitive inhibition.

However if this is for a specific example where you have observed the antagonist having higher affinity then these are the points you need to consider:
The concentrations
The mode of inhibition (for example does the antagonist covalently bind to the receptor?)
The binding mode in general, how strong is the ligand receptor interaction- which forces/bonds are involved? For example if your receptor pocket was very positive perhaps you antagonist would be more negatively charged than your agonist to cause it not to dissociate as readily when bound.
Also consider how the antagonist works- is it competitive or allosteric? Or does it just block an ion channel?

Hmm I don't know how well I have explained this so if it makes no sense feel free to post back what's wrong! Also I can't tell if you want an answer for a specific problem or you are looking for a more general guide. Hope this gets the ball rolling anyway :)