Edaravone, a member of the substituted 2-pyrazolin-5-one class, has the chemical name
3-methyl-1-phenyl-2-pyrazolin-5-one. It is a white crystalline powder and is freely soluble in acetic acid,
methanol, or ethanol, as well as slightly soluble in water or diethyl ether. Edaravone is available as a clear,
colorless liquid provided as a sterile injection solution supplied for intravenous (IV) infusion. The structure of
edaravone is showed in figure 1.
Fig. 1 Structure of edaravone
Function of Edaravone in the treatment of amyotrophic lateral sclerosis
Introduction of amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases. ALS belongs to a wider group of
disorders known as motor neuron diseases, which are caused by gradual deterioration (degeneration) and death of
motor neurons. Motor neurons are nerve cells that extend from the brain to the spinal cord and to muscles throughout
the body. These motor neurons initiate and provide vital communication links between the brain and the voluntary
muscles. The disease is progressive, meaning the symptoms get worse over time.
Fig. 2 The symptoms of ALS
Treatments can't reverse the damage of amyotrophic lateral sclerosis, but they can slow the progression of symptoms,
prevent complications, and make you more comfortable and independent.
Edaravone was approved in Japan in 2015, and in the U.S. in 2017, based primarily on positive results of a single
clinical trial in early-stage ALS patients conducted in Japan.
Edaravone has been available in Japan since 2003 for the treatment of acute stroke, but also showed promise in mouse
models for ALS. An initial randomized controlled trial in patients with ALS did not show benefit for all patients,
although a subgroup of patients in the earliest disease phase did benefit. A subsequent trial compared edaravone
plus riluzole versus riluzole alone in patients with early-stage ALS who were free of substantial respiratory muscle
weakness and who had progressed over a 3-month observation period. This study showed a 33% slowing in the rate of
disease progression over a 6-month treatment period [1].
Mechanism of action
Nootropic and neuroprotective effects are mediated through inhibiting lipid peroxidation and scavenging free
radicals. Free radicals are byproducts of normal cellular processes that produce energy. Normally, the body quickly
removes them. If they remain in the body, they can cause oxidative stress, leading to damage and cell death. Researchers think that oxidative stress due to free radicals is one of the causes of nerve cell death in ALS. Edaravone acts to increase prostacyclin production, decrease lipoxygenase metabolism of arachidonic acid by trapping
hydroxyl radicals, and inhibit alloxan-induced lipid peroxidation and quench active oxygen species. It targets
various kinds of cells, including neurons, endothelial cells and myocardial cells.
Side effects
In U.S. clinical trials and in post-marketing data from outside the U.S., the most serious adverse effects reported
with edaravone treatment included hypersensitivity and sulfite allergic reactions, including anaphylactic symptoms.
Bruising or contusions, gait disturbance, headache, dermatitis, and eczema were the most common adverse reactions
observed in 10% or greater of edaravone-treated patients during the studies. The adverse reactions that occurred in
2% or more of edaravone-treated patients and at least 2% more frequently than in the placebo group appear in Table 1 [2].
Alfa Chemistry offers high quality of edaravone which meets the CP standards. Please feel free to contact us for APIs or technical services.
References
Ari Breiner, Lorne Zinman, and Pierre R. Bourque. Edaravone for amyotrophic lateral sclerosis: barriers to
access and lifeboat ethics. Canadian Medical Association Journal, 2020, 192(12): E319–E320.
Dr. Cruz. Edaravone (Radicava) A Novel Neuroprotective Agent for the Treatment of Amyotrophic Lateral Sclerosis.
P T. 2018 Jan; 43(1): 25–28.
