Inhibitors of Catechol-O-methyltransferase in the Treatment of Neurological Disorders
2014
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.
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