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Mechanisms of involvement of Eicosanoids and their precursors in the pathophysiology and treatment of schizophrenia


Schmidt, L and Ceglarek, U and Kortz, L and Hoop, M and Kirkby, KC and Thiery, J and Himmerich, H, Mechanisms of involvement of Eicosanoids and their precursors in the pathophysiology and treatment of schizophrenia, Medicinal Chemistry, 9, (6) pp. 763-73. ISSN 1573-4064 (2013) [Refereed Article]

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Copyright 2013 Bentham Science Publishers

DOI: doi:10.2174/1573406411309060002


The pathophysiology of schizophrenia has not been fully elucidated but there are converging leads to understanding this complex psychiatric disorder. One family of molecules that may play a crucial role in the development of schizophrenia is the eicosanoids. Review of the literature on eicosanoids in patients with schizophrenia points to findings in three areas: precursor molecules such as polyunsaturated fatty acids (PUFAs) and specifically arachidonic acid (AA), the actions of specific eicosanoids such as thromboxane A2 (TxA2), thromboxane B2 (TxB2) and prostaglandin E2 (PGE2), and enzymes with important functions in eicosanoid metabolism such as cyclooxygenase 2 (COX-2).

It has also been found that classical as well as second generation antipsychotics, drugs used to treat schizophrenia, influence eicosanoid metabolism. For example, clozapine and its metabolite N-desmethylclozapine (NDMC) decreased TxB2 production in vitro.

Eicosanoids and the enzymes involved in their metabolism may provide novel future drug targets. Therapeutic response to COX-2 inhibitors has already been demonstrated in patients at an early stage of schizophrenia. COX-2 inhibitors may exert this therapeutic action through their effects in reducing PGE2, type-2 cytokine and kynurenic acid production and strengthening glutamatergic neurotransmission.

Item Details

Item Type:Refereed Article
Keywords:schizophrenia, antipsychotics, thromboxane A2, thromboxane B2
Research Division:Health Sciences
Research Group:Health services and systems
Research Field:Mental health services
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Mental health
UTAS Author:Kirkby, KC (Professor Kenneth Kirkby)
ID Code:87284
Year Published:2013
Web of Science® Times Cited:10
Deposited By:Medicine
Deposited On:2013-11-12
Last Modified:2017-11-06

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