Phentolamine (DB00692): A Comprehensive Pharmacological and Clinical Monograph

Introduction and Overview

Phentolamine is a potent, reversible, non-selective alpha-adrenergic receptor antagonist belonging to the imidazoline class of chemical compounds.[1] Its clinical history represents a compelling narrative of pharmacological evolution and therapeutic repurposing. Initially introduced for the systemic management of hypertension, this application was ultimately curtailed due to a significant burden of cardiovascular and gastrointestinal adverse effects associated with chronic, large oral doses.[1] Despite this early setback, the potent and rapid vasodilatory properties of phentolamine secured its role as a critical, life-saving agent for the management of acute hypertensive emergencies, most notably those arising from the catecholamine excess characteristic of pheochromocytoma.[3]

The therapeutic journey of phentolamine serves as a classic paradigm of drug repurposing in modern medicine. The same powerful systemic effects that proved problematic for chronic therapy have been ingeniously harnessed for niche, localized applications where the benefit-risk profile is exceptionally favorable. This strategic shift is exemplified by the development of two highly successful formulations: OraVerse, an injectable solution for the reversal of soft-tissue anesthesia in dentistry, and Ryzumvi, an ophthalmic solution for the reversal of pharmacologically-induced mydriasis.[2] These innovations have transformed phentolamine from a specialized hospital-based emergency drug into a valuable tool in outpatient and specialty clinic settings.