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Benserazide hydrochloride (benserazide HCl) is a peripherally-acting aromatic L-amino acid decarboxylase (AADC) or DOPA decarboxylase (DDC) inhibitor. It is unable to cross the blood-brain barrier, allowing it to selectively inhibit the conversion of levodopa to dopamine in the peripheral circulation. This increases the amount of levodopa that can cross into the central nervous system and reduces peripheral side effects such as nausea and arrhythmias. Benserazide HCl is widely used in combination with levodopa (as co-beneldopa) under brand names like Madopar and Prolopa for the treatment of Parkinson's disease and restless legs syndrome. Additionally, benserazide HCl is being investigated as a single agent in Phase 1/2 clinical trials for the treatment of beta-thalassemia and sickle cell disease due to its ability to induce fetal hemoglobin (HbF) expression. Preclinical research also suggests potential applications in oncology, particularly melanoma, through the inhibition of pyruvate kinase M2 (PKM2) and cystathionine beta-synthase (CBS).
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