A Comprehensive Monograph on Minoxidil (DB00350): From Antihypertensive Agent to Alopecia Therapeutic

Executive Summary

Minoxidil (DrugBank ID: DB00350) represents a remarkable case study in pharmaceutical serendipity and repurposing. Initially developed as a potent oral antihypertensive agent, its clinical journey was unexpectedly redirected by the observation of a prominent side effect: hypertrichosis. This led to its reinvention as a ubiquitous topical treatment for androgenetic alopecia. This monograph provides a comprehensive analysis of Minoxidil, detailing its chemical properties, multifaceted mechanism of action, and the distinct clinical profiles of its oral and topical formulations. As a prodrug, Minoxidil's efficacy is contingent upon its conversion to the active metabolite, minoxidil sulfate, a process catalyzed by sulfotransferase enzymes. The variability in this enzymatic activity, particularly within hair follicles, is a key determinant of patient response to topical therapy. The oral formulation (Loniten®) remains a last-line agent for severe, refractory hypertension due to a significant risk of serious cardiovascular adverse effects, underscored by an FDA Black Box Warning. Conversely, the topical formulations (Rogaine® and generics) have a favorable safety profile, enabling over-the-counter availability. Emerging clinical practice is now revisiting the oral route with low-dose regimens for alopecia, aiming to bypass the limitations of topical application in a strategy that brings the drug's history full circle.

Section 1: Chemical and Pharmaceutical Profile

This section establishes the fundamental identity of Minoxidil, providing a comprehensive overview of its chemical structure, properties, synthesis, and the various formulations available to clinicians and consumers.

1.1. Identification and Nomenclature