Inhibitors of Catechol-O-methyltransferase in the Treatment of Neurological Disorders

Author(s): Nidhi Jatana, N. Apoorva, Sonika Malik, Aditya Sharma, Narayanan Latha

Journal Name: Central Nervous System Agents in Medicinal Chemistry
Formerly Current Medicinal Chemistry - Central Nervous System Agents

Volume 13 , Issue 3 , 2013

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Catechol-O-methyltransferase (COMT) is the enzyme which catalyzes the transfer of a methyl group from S-adenosylmethionine 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.

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Article Details

Year: 2013
Published on: 24 April, 2014
Page: [166 - 194]
Pages: 29
DOI: 10.2174/1871524913666140109113341
Price: $65

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