Kinetic Study of Radical-Scavenging and Vitamin E-Regenerating Actions of Edaravone (3-Methyl-1-phenyl-2-pyrazolin-5-one)

A kinetic study was performed for edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) in order to clarify the mechanism of its free-radical-scavenging and vitamin E-regenerating actions. The second-order rate constants for the radical-scavenging reaction of edaravone were measured in several organic solvents and in a water/methanol mixed solvent at various pH. The keto–enol tautomerism and the acid–base dissociation equilibrium of edaravone produce keto, enol, and anion forms in solutions, and their contributions and activities varied depending on the properties of the solutions. From the results of NMR and kinetic studies, it has been clarified that the keto–enol tautomerism of edaravone actually exists, and the keto form has larger radical-scavenging activity than the enol form. Furthermore, the pH dependence of the rate constants suggests that the anion form produced by the acid–base dissociation equilibrium of edaravone has the highest radical-scavenging activity in the keto, enol, and anion forms.