Effects of a New Natural Catechol-O-methyl Transferase Inhibitor on Two In Vivo Models of Parkinson’s Disease

• DOI: 10.1021/acschemneuro.2c00356
• Publication Date: 2022-11-08T22:04:41Z
• Authors: Valeria Parrales-...; Abha Harfouche; Laurent Ferrié; Stéphane Haïk; Patrick P. Michel; Rita Raisman-Vozari; Bruno Figadère; Nicolas Bizat; Alexandre Maciuk
• Keywords: Catechol; Transferase

A tetrahydroisoquinoline identified in Mucuna pruriens ((1R,3S)-6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline-1,3-dicarboxylic acid, compound 4) was synthesized and assessed for its vitro pharmacological profile vivo effects two animal models of Parkinson's disease. Compound 4 inhibits catechol-O-methyltransferase (COMT) with no affinity the dopaminergic receptors or dopamine transporter. It restores dopamine-mediated motor behavior when it is co-administered L-DOPA to C. elegans worms 1-methyl-4-phenylpyridinium-damaged neurons. In a 6-hydroxydopamine rat model disease, co-administration at 30 mg/kg enhances effect an intensity similar that tolcapone 1 but shorter duration. The not dose-dependent. seems cross blood-brain barrier thus acts as peripheral COMT inhibitor. inhibition by further validates traditional use M. treatment can be considered promising drug candidate development safe, inhibitors.