A novel compound is co-administered with a full agonist acting at the same receptor. The concentration-response curve of the agonist now reaches a maximum effect substantially lower than before, even when the agonist dose is raised greatly. Which type of interaction best explains this observation?

• A Irreversible (noncompetitive) antagonism ✓
• B Reversible competitive antagonism
• C Partial agonist competition at spare receptors only
• D Physiological antagonism through a separate receptor system

Explanation

An irreversible antagonist binds covalently or dissociates extremely slowly, effectively removing receptors from the pool. Because no amount of additional agonist can restore the lost receptor reserve once it is depleted, the maximum achievable effect falls while the EC50 may remain near normal. B reversible competitive antagonist instead produces a parallel rightward shift with unchanged Emax, which is exactly what this scenario rules out.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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