An antagonist interacts with the agonist-binding domain of a receptor and blocks the agonist from interacting with it. Antagonism may be reversible or irreversible. A reversible antagonist binds to the agonist-binding domain of the receptor, but high concentrations of the agonist can overcome the antagonism. Naloxone is a reversible (competitive) antagonist at opioid receptor sites. An irreversible antagonist also blocks the agonist-binding domain, but forms a permanent drug-receptor bond (i.e., covalent bond), which is irreversible (noncompetitive).

An allosteric antagonist binds to a receptor at a site other than the agonist-binding domain and produces a conformational change in the receptor. This either alters the Kd for the agonist or inhibits the receptor from responding to the agonist. There are also two non-receptor-related mechanisms of antagonism. A chemical antagonist sequesters the agonist and prevents it from interacting with its receptor. A physiologic antagonist blocks the action of an agonist by a molecular mechanism that does not involve the receptor for that agonist.