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CNS & Neurological Disorders - Drug Targets


ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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

Author(s): Colm M.P. O’Tuathaigh, Lieve Desbonnet, Peter Lee and John L. Waddington

Volume 11 , Issue 3 , 2012

Page: [282 - 291] Pages: 10

DOI: 10.2174/187152712800672418

Price: $65


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.

Keywords: Catechol-O-methyltransferase, schizophrenia, antipsychotics, cognition, negative symptoms, Psychotic illness, 22q11-deletion syndrome, Valine, Mrthionine, Cannabis

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