A Comprehensive Monograph on Hydralazine (DB01275): From Molecular Mechanisms to Clinical Applications

Introduction and Historical Context

Overview

Hydralazine (DrugBank ID: DB01275) is a small molecule, direct-acting peripheral arteriolar vasodilator that has occupied a distinct and evolving position in the cardiovascular pharmacopoeia for over seven decades.[1] Its primary therapeutic applications include the management of essential hypertension, particularly cases refractory to other agents; the treatment of severe hypertension, including hypertensive emergencies and crises associated with pregnancy (pre-eclampsia/eclampsia); and as a crucial component of adjunctive therapy in heart failure with reduced ejection fraction.[1] Despite its long history and proven efficacy in specific contexts, Hydralazine is no longer considered a first-line agent for most of these indications. Its clinical utility is tempered by a challenging side-effect profile, most notably a reflex sympathetic stimulation of the heart, and the development of newer, better-tolerated antihypertensive medications with more convenient dosing regimens.[1]

Discovery and Development

The discovery of Hydralazine is a classic example of serendipity in pharmaceutical research. In the late 1940s, scientists at the Swiss pharmaceutical company Ciba (later Ciba-Geigy, now part of Novartis) were investigating a series of hydrazine-phthalazine derivatives, initially in search of a novel treatment for malaria.[1] During this investigation, one compound, then designated C-5968, demonstrated potent blood pressure-lowering capabilities.[5] Recognizing its potential, Ciba repurposed the compound, filing a patent in 1945 which was issued in 1949.[5] The name "hydralazine" first appeared in the literature between 1950 and 1955.[6]