Propranolol: A Comprehensive Monograph on a Foundational Beta-Adrenergic Antagonist

Introduction: Propranolol - A Paradigm-Shifting Pharmacological Agent

Executive Summary

Propranolol is the prototypical non-selective beta-adrenergic receptor antagonist, a cornerstone medication that has fundamentally shaped the management of a wide spectrum of cardiovascular and non-cardiovascular disorders for over half a century.[1] Identified by its DrugBank accession number DB00571 and Chemical Abstracts Service (CAS) number 525-66-6, propranolol operates through the competitive, non-selective blockade of beta-1 (

β1​) and beta-2 (β2​) adrenergic receptors.[3] This mechanism of action allows it to effectively treat conditions ranging from hypertension, angina pectoris, and cardiac arrhythmias to migraine prophylaxis and essential tremor.[3] First granted approval by the U.S. Food and Drug Administration (FDA) on November 13, 1967, it has since become a widely prescribed generic medication, with over 8 million prescriptions in the United States in 2022 alone, underscoring its enduring clinical importance and widespread utility.[1]

Historical Context and the Dawn of Rational Drug Design

The development of propranolol represents a landmark achievement in modern pharmacology, not only for the therapeutic benefits it conferred but also for the revolutionary scientific methodology it validated. The drug was discovered by the Scottish pharmacologist Sir James Whyte Black at Imperial Chemical Industries (ICI) Pharmaceuticals, patented in 1962, and approved for medical use in 1964.[1] Sir James Black's research was profoundly influenced by personal experience; the death of his father from a heart attack during his time in medical school is thought to have catalyzed his focus on developing drugs to protect the heart from the deleterious effects of stress hormones.[6]