Mechanism of Action of Metaraminol
Metaraminol is a sympathomimetic agent that acts primarily as an alpha-1 adrenergic receptor agonist, causing direct vasoconstriction, with additional indirect effects through stimulation of endogenous norepinephrine release. 1
Primary Mechanism
Metaraminol functions as a direct alpha-1 selective adrenergic agonist, producing therapeutic vasoconstriction within peripheral vasculature by activating alpha-adrenergic receptors on vascular smooth muscle. 1
The drug also has indirect sympathomimetic actions that stimulate endogenous norepinephrine release, resulting in mixed alpha and beta-adrenergic effects, though the alpha-mediated vasoconstriction predominates. 1
Hemodynamic Effects
Metaraminol increases systemic vascular resistance (SVRI) as its primary hemodynamic effect, which is the mechanism by which it restores blood pressure in hypotensive states. 2
In comparative studies, metaraminol was more effective than colloid volume expansion because it directly increased SVRI, whereas colloid increased central venous pressure without significantly increasing cardiac index. 2
The drug causes marked increases in arterial pressure, pulmonary arterial pressure, wedge pressure, and central venous pressure, with calculated increases in stroke volume, left and right ventricular stroke work, and cardiac work. 3
Clinical Pharmacology Context
Unlike phenylephrine (which is purely alpha-1 selective with no indirect neurotransmitter-releasing action), metaraminol has both direct alpha receptor activation and indirect norepinephrine release, potentially increasing the risk of cardiovascular side effects including hypertension, tachycardia, palpitations, and cardiac arrhythmias. 1
Metaraminol demonstrated a 70% resolution rate for ischemic priapism in pooled data, which was attributed to its alpha receptor-mediated vasoconstriction within the corpora cavernosa. 1
Important Clinical Considerations
The mixed alpha and beta effects from indirect norepinephrine release mean metaraminol carries greater cardiovascular risk compared to pure alpha-1 agonists like phenylephrine, particularly regarding hypertensive effects and cardiac chronotropic/inotropic stimulation. 1
Metaraminol is widely used as a peripheral vasopressor in ICU settings, particularly as first-line therapy in less severely ill patients, with median infusion rates of 4.0 mg/h and durations around 7-10 hours. 4, 5
The drug has been used successfully in cardiac arrest caused by anaphylaxis as an alpha-1 receptor agonist alternative when standard therapy fails, though evidence is limited to case reports. 1