The Novel Antioxidant Edaravone: From Bench to Bedside

Abstract

Over the last decade, important advances have been made to support the fact that reactive oxygen species (ROS) are generated and play a harmful role during the acute and late stages of cerebral ischemia. Several drugs, such as radical scavengers and antioxidants, have been evaluated in preclinical and clinical studies. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut R , Mitsubishi Tanabe Pharma Corporation) is a novel antioxidant that is currently used in Japan for the treatment of patients in the acute stage of cerebral infarction. Edaravone scavenges ROS and inhibits proinflammatory responses after brain ischemia in animals and humans. In particular, postischemic inflammation, leading to brain edema and infarction due to neuronal damage and endothelial cell death, can be ameliorated by edaravone. In addition to these antistroke effects, edaravone has also been shown to prevent oxidative damage to various extracerebral organs. Therefore, in addition to its usefulness in the treatment of stroke, edaravone is expected to play an integral role in the treatment of many oxidative stress-related diseases.

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“…Therefore, the good thing about the antioxidant drugs is that once they are developed for one disease, they can also be potentially useful for other apparently dissimilar pathologies. Edaravone has been used successfully in animal models of extracerebral diseases such as amyotrophic lateral sclerosis (ALS) [70] ischemic injury to spinal cord, kidney and intestine and a number of other pathologies (reviewed by Watanabe and colleagues [51]. It has also shown beneficial effects in human studies; It was able to prevent cerebral hyperperfusion after carotid endarterectomy [71] and decreased reperfusion injury in acute myocardial infarction patients [72] (reviewed by Higashi and coworkers [73].…”

“…Edaravone was developed in the process of searching for "phenol-like" compounds with antioxidant properties. This pyrazolin containing molecule undergoes keto-enol tautomerization and generates phenolic structure [51]. Half of edaravone exists in an anionic form at physiological pH, which is the form that strongly reacts with the ROS in the brain [52].…”

“…Edaravone has shown in vitro antioxidant activity against ROS such as singlet oxygen [54], hydroxyl radical [55,56] and other ROS [57]. Edaravone has been reported to reduce oxidative damage in rodents' brain after ischemic injury [58] (reviewed by Watanabe and colleagues [51]). …”

“…However, around 500,000 of stroke patients have been treated with this drug, which provides a very good level of post-marketing experience [51].…”

“…(2)) initially developed by Mitsubishi Tanabe Pharma Corporation (Osaka, Japan) has been approved in Japan since 2001 for reduction of neuronal damage after acute ischemic stroke [51]. Edaravone was developed in the process of searching for "phenol-like" compounds with antioxidant properties.…”