What Antagonists Do to the Curve

potency

shifting the curve horizontally

efficacy

shifting the curve vertically

Competitive Reversible Antagonists

Parallel rightward shift

Non-Competitive / Irreversible Antagonists

Downward squash

Uncompetitive Antagonists

Shifts down and to the left

Physiological (Functional) Antagonists

Depresses the overall physiological response curve without competing for the same molecular target

Chemical Antagonists

Flattens or eliminates the agonist curve by drastically reducing the concentration of active free drug.

Competitive Reversible

Binding Site: Active site

Can be overcome by ↑ Agonist?: Yes

EC50​ (Potency): Increased ( ↑ )

Emax (Efficacy): No change

Curve Shift: Rightward

Non-Competitive / Irreversible

Binding Site: Active or Allosteric

Can be overcome by ↑ Agonist?: No

EC50​ (Potency): No change

Emax (Efficacy): Decreased (↓)

Curve Shift: Downward

Uncompetitive

Binding Site: Agonist-Receptor Complex

Can be overcome by ↑ Agonist?: No

EC50​ (Potency): Decreased (↓)

Emax (Efficacy): Decreased (↓)

Curve Shift: Down & Left

Physiological

Binding Site: Separate Receptor

Can be overcome by ↑ Agonist?: No

EC50​ (Potency): N/A

Emax (Efficacy): Decreased (↓)

Curve Shift: Functional depression

Chemical

Binding Site: Direct to Drug Molecule

Can be overcome by ↑ Agonist?: No

EC50​ (Potency): N/A

Emax (Efficacy): Decreased (↓)

Curve Shift: Dose-dependent drop

Competitive Reversible: example

Atropine competing with Acetylcholine at muscarinic receptors; Naloxone competing with Morphine at mu-opioid receptors.

Non-Competitive / Irreversible: example

Phenoxybenzamine covalently blocking $\alpha$-adrenergic receptors; Aspirin irreversibly inhibiting COX enzymes.

Uncompetitive Antagonists: example

Memantine blocking NMDA receptors only when excessively activated by glutamate.

Physiological (Functional) Antagonists: example

Epinephrine (beta2 receptors → bronchodilation) counteracting Histamine (H1 receptors → bronchoconstriction) during anaphylaxis.

Chemical Antagonists: example

Protamine sulfate binding Heparin; Sugammadex chelating Rocuronium; Digibind neutralizing Digoxin