Is norepinephrine an agonist or antagonist?

Norepinephrine's Pharmacological Classification

Norepinephrine is primarily an agonist that acts on both alpha and beta adrenergic receptors, with predominant alpha-adrenergic effects causing vasoconstriction.

Receptor Activity Profile

Norepinephrine functions as:

• Alpha receptor agonist: Strong affinity for alpha-adrenergic receptors, particularly alpha-1 receptors 1
• Beta receptor agonist: Also acts on beta-1 adrenergic receptors, but with less potency than its alpha effects 1, 2

Detailed Receptor Actions

1. Alpha-adrenergic effects (predominant action):

   • Causes potent peripheral vasoconstriction 1
   • Increases systemic vascular resistance 1
   • Used clinically to increase blood pressure in hypotensive states 1

2. Beta-adrenergic effects (secondary action):

   • Stimulates beta-1 receptors in the heart, causing:
     • Mild to moderate increases in heart rate (less than epinephrine) 1
     • Increased cardiac contractility 1
   • Can produce peripheral beta-1 adrenergic vasodilation when alpha effects are blocked 2

Comparison with Other Catecholamines

Agent	Alpha Effects	Beta-1 Effects	Beta-2 Effects	Clinical Use
Norepinephrine	+++ (strong)	++ (moderate)	Minimal	Vasopressor for shock with low SVR [1]
Epinephrine	++	+++	+++	Cardiac arrest, anaphylaxis [1]
Dobutamine	Minimal	+++	+	Cardiogenic shock without hypotension [3]

Clinical Applications

Norepinephrine is primarily used as a vasopressor in:

• Distributive shock (first-line agent) 3
• Septic shock with low systemic vascular resistance 1
• Cardiogenic shock (with caution) when combined with dobutamine 1

Dosing Considerations

• Typical dosing range: 0.2 to 1 mcg/kg/min 1
• Requires careful titration to achieve desired blood pressure
• Should be administered through central venous access when possible

Important Considerations

• Norepinephrine may reduce end-organ perfusion due to its potent vasoconstrictive effects 1
• In cardiogenic shock, excessive vasoconstriction may increase cardiac afterload and worsen heart failure 1
• Monitoring of blood pressure, heart rate, and tissue perfusion is essential during administration
• When used in right ventricular failure, norepinephrine helps maintain coronary perfusion pressure while supporting contractility 3

Norepinephrine's classification as an agonist (rather than antagonist) is clearly established across all authoritative guidelines, with its primary mechanism being direct stimulation of adrenergic receptors to produce physiological effects 4, 5, 6.