Abstract
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.
Keywords: Schizophrenia, antipsychotics, thromboxane A2, thromboxane B2.
Medicinal Chemistry
Title:Mechanisms of Involvement of Eicosanoids and their Precursors in the Pathophysiology and Treatment of Schizophrenia
Volume: 9 Issue: 6
Author(s): Luise Schmidt, Uta Ceglarek, Linda Kortz, Marcus Hoop, Kenneth Clifford Kirkby, Joachim Thiery and Hubertus Himmerich
Affiliation:
Keywords: Schizophrenia, antipsychotics, thromboxane A2, thromboxane B2.
Abstract: 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.
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Cite this article as:
Schmidt Luise, Ceglarek Uta, Kortz Linda, Hoop Marcus, Kirkby Clifford Kenneth, Thiery Joachim and Himmerich Hubertus, Mechanisms of Involvement of Eicosanoids and their Precursors in the Pathophysiology and Treatment of Schizophrenia, Medicinal Chemistry 2013; 9 (6) . https://dx.doi.org/10.2174/1573406411309060002
DOI https://dx.doi.org/10.2174/1573406411309060002 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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