Receptor Antagonist
A receptor antagonist binds a receptor without activating it, producing its effect entirely by preventing an agonist — usually the endogenous ligand — from signalling there.
An antagonist occupies a receptor and generates no signal of its own; its intrinsic efficacy is zero. Everything it does is subtraction, so its effect is visible only where there is something to subtract. Competitive antagonists bind the orthosteric site reversibly and can be overcome by raising agonist concentration, shifting the curve rightward without lowering its ceiling. Non-competitive and irreversible antagonists cannot be outcompeted and lower the achievable maximum instead.
Peptide antagonists are well represented. Cetrorelix and ganirelix block the GnRH receptor directly and are used in assisted reproduction precisely because they suppress an LH surge without the flare a GnRH agonist causes first. Pegvisomant, approved in 2003 for acromegaly, is a modified growth hormone molecule that binds the GH receptor but cannot complete the dimerisation needed to signal, so IGF-1 falls while GH itself stays high.
Because an antagonist only removes existing tone, the size of its effect depends on how much tone there is. The same dose does little in a quiet system and a great deal in an activated one, which is why antagonist effects are larger under stress or in disease than in a resting healthy subject. It also means a measured IC50 depends on the agonist concentration tested against.
Two misreadings recur. The first is that blockade switches the pathway off, when at achievable concentrations only a fraction of receptors is occupied and signalling is reduced, not abolished. The second is labelling as an antagonist a compound that is really an inverse agonist, suppressing constitutive activity below baseline. Separating them needs a system with measurable basal tone, which many screening assays lack.