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Catechol-O-Methyl Transferase as a Drug Target for Schizophrenia

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Current antipsychotic drugs lack material efficacy against the negative symptoms and cognitive deficits of schizophrenia. There is considerable uncertainty regarding the optimal pharmacotherapeutic strategy for treating these and other aspects of psychotic illness. The present review summarises clinical, mutant, and psychopharmacological data related to catechol-O-methyltransferase (COMT), an enzyme involved in the catabolism of catecholamine neurotransmitters, with a view to establishing the antipsychotic potential of compounds targeting the action of this enzyme. The review examines clinical and preclinical genetic data linking COMT gene variation with risk for schizophrenia or specific symptoms or disease endophenotypes. We then summarise data concerning the behavioural effects of COMT inhibitors. These genetic and pharmacological data relating to COMT as a therapeutic target have implications for the development of individualised treatments for treatment-resistant symptoms of schizophrenia, including cognitive dysfunction and, potentially, negative symptoms.
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Keywords: 22q11-deletion syndrome; Cannabis; Catechol-O-methyltransferase; Mrthionine; Psychotic illness; Valine; antipsychotics; cognition; negative symptoms; schizophrenia

Document Type: Research Article

Affiliations: School of Medicine, University College Cork, Cork, Ireland.

Publication date: 2012-05-01

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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