Norepinephrine (DB00368): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Norepinephrine, also known as noradrenaline, is an endogenous catecholamine that functions as a primary neurotransmitter of the sympathetic nervous system and as a hormone released by the adrenal medulla. In its therapeutic form, norepinephrine is a potent sympathomimetic medication, indispensable in critical care medicine for the management of life-threatening hypotension. It is identified by DrugBank ID DB00368 and CAS Number 51-41-2.[1]

Pharmacologically, norepinephrine exerts its effects through potent agonism at alpha-1 (α1​) and beta-1 (β1​) adrenergic receptors, with minimal activity at beta-2 (β2​) receptors.[2] Its primary mechanism of action involves intense peripheral vasoconstriction mediated by

α1​ receptors, leading to a significant increase in systemic vascular resistance (SVR) and, consequently, mean arterial pressure (MAP). Concurrently, its β1​ receptor activity provides positive inotropic effects, enhancing myocardial contractility.[1] This dual action makes it uniquely effective in treating vasodilatory shock states.

The clinical application of norepinephrine is firmly established, with the Surviving Sepsis Campaign guidelines recommending it as the first-line vasopressor for septic shock unresponsive to fluid resuscitation.[2] Evidence from multiple meta-analyses demonstrates its superiority over dopamine in this setting, primarily due to a lower incidence of cardiac arrhythmias and a potential mortality benefit.[1] Its role in other shock states, particularly cardiogenic shock, remains a subject of clinical investigation and debate, as the increase in afterload may elevate myocardial oxygen demand in an already compromised heart.[2]