Let's say we have drug X, which is a full agonist at receptor A and a partial agonist at receptor B. We also have drug Y, which has no affinity for receptor A, but is a potent full antagonist at receptor B. We're also going to say that there's only a single site at both receptors, so that X and Y compete for the same sites. The last assumption is that only receptor A modulates the clinically relevant response.
Would the measured response be appreciably greater if we were to add both X and Y, compared to the response of the same concentration of X alone?
I'm wondering, since blocking the binding of drug X to receptor B should lead to a larger number of molecules of drug X to be available for binding to receptor A. My immediate thought is that it in reality shouldn't lead to an appreciably larger response. I'm thinking this simply because in the book Rang and Dale's Pharmacology, 7th ed. (p. 17), one of the assumptions is that the amount of unbound drug is much larger than the amount of bound drug, such that any binding or "un-binding" shouldn't affect the concentration of the drug to any significant degree. However, if the amount of B-receptors is a lot higher than the amount of A-receptors, blocking all the B-receptors should, at least in my mind, lead to many more A-receptors being activated, such that the response would become larger. But are there any clinically relevant examples of this? For example, two receptors where one is highly expressed in the tissue, while the other receptor is only slightly expressed?
(Since this is my first post here, please correct me if I've violated any of the rules with regards to type of question and formatting and such.)