Edaravone (DB12243): A Comprehensive Monograph on its Pharmacology, Clinical Efficacy, and Therapeutic Applications

Executive Summary

Edaravone is a small molecule, pyrazolone-derivative compound that has emerged as a significant therapeutic agent in the management of select neurodegenerative and neurovascular conditions. Initially developed and approved for acute ischemic stroke in Japan, its therapeutic scope has expanded to include amyotrophic lateral sclerosis (ALS), a progressive and fatal motor neuron disease. This report provides an exhaustive analysis of Edaravone, cataloging its molecular characteristics, pharmacological profile, clinical development, and therapeutic applications.

The primary mechanism of action of Edaravone is its function as a potent free radical scavenger. It effectively neutralizes highly reactive oxygen species (ROS), such as hydroxyl radicals and peroxynitrite, which are key mediators of oxidative stress-induced cellular damage. This antioxidant activity is the mechanistic foundation for its neuroprotective effects, as it mitigates lipid peroxidation of cell membranes, suppresses downstream inflammatory cascades, and inhibits apoptotic pathways in neuronal and vascular endothelial cells.

Clinically, Edaravone holds a unique dual-indication status. In Japan, it has been used since 2001 for the treatment of acute ischemic stroke, where it is administered to limit the reperfusion injury that follows a cerebrovascular event. Its approval for ALS by the U.S. Food and Drug Administration (FDA) in 2017 marked a landmark development, making it the first new treatment for the disease in over two decades. This approval was based on the pivotal MCI186-19 clinical trial, which demonstrated a statistically significant 33% slowing in the rate of functional decline in a carefully selected subpopulation of ALS patients.