Neurological and psychiatric management using COMT inhibitors: A review

The increase in psychiatric and neurological disorders includes Parkinson's, Schizophrenia, Alzheimer's and Depression over the last 50 years adds concerns to society. In contrast, there have been great advances in elucidating the receptors of CNS and their interaction with the novel molecules. Enzymes inhibitors are on the top plan to interact specifically with the targets for better potency and reduce the toxic effects. COMT inhibitors work by inhibiting the conversion of catechols including dopamine to its inactive degradation products. This makes the availability of l-dopa to the brain and thus alleviating the symptoms of CNS disorders. Substitution pattern and the structural requirements for better binding within the receptors are important for the drug findings. Apart from catechol modification, some non-catechol based potent COMT inhibitors are also discussed. A detailed guide regarding inhibition of S-adenosyl-l-methionine, catalyzing the transfer of the methyl group by COMT is also represented. This review discusses the thorough development of COMT inhibitors right from the beginning until the present. The derivatives are discussed along with their structure-activity relationship having structural substitution prerequisites for the development of more potent novel COMT inhibitors.