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

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

Volume: 11 Issue: 3

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

Affiliation:

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

Abstract: 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.

Cite this article as:

M.P. O’Tuathaigh Colm, Desbonnet Lieve, Lee Peter and L. Waddington John, Catechol-O-Methyl Transferase as a Drug Target for Schizophrenia, CNS & Neurological Disorders - Drug Targets 2012; 11 (3) . https://dx.doi.org/10.2174/187152712800672418