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Central Nervous System Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Central Nervous System Agents)
ISSN (Print): 1871-5249
ISSN (Online): 1875-6166
Epub Full Text Article
DOI: 10.2174/1871524913666140109113341      Price:  $95









Inhibitors of Catechol-O-Methyl Transferase in the Treatment of Neurological Disorders

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Author(s): Nidhi Jatana, N. Apoorva, Sonika Malik, Aditya Sharma and N. Latha
Abstract:
Catechol-O-methyltransferase (COMT) is the enzyme which catalyzes the transfer of a methyl group from Sadenosylmethionine to catechols and catecholamines, like the neurotransmitters dopamine, epinephrine and norepinephrine. COMT has implications in many neurological and psychiatric disorders like schizophrenia, Parkinson’s disease (PD), bipolar disorders, etc. and therefore, it serves as an important drug target. Since its characterization in 1957, many inhibitors were designed where the first generation inhibitors were found to be highly toxic, short acting and had poor bioavailability. Currently, two of the second generation inhibitors, tolcapone and entacapone have been used for treatment of PD but are associated with various dopaminergic and gastro-intestinal side-effects. There have been several approaches for the design of novel COMT inhibitors with a good and safe therapeutic profile. The focus of this article is to review the current knowledge on COMT and the role of COMT inhibitors in the treatment of neurological disorders. The inhibitors have been classified into six different classes based on the structural framework. A historical overview of the discovery and development of COMT inhibitors is presented with a special emphasis on new generation of inhibitors till date
Keywords:
Catechol-O-methyltransferase (COMT), COMT Isoforms, V108M Polymorphism, Structure of COMT, COMTInhibitors, Classification of COMT-Inhibitors
Affiliation:
Bioinformatics Infrastructure Facility, Sri Venkateswara College, Benito Juarez Road, Dhaula Kuan, New Delhi 110021, India