Mechanisms of action of the mood stabilizer valproate: A focus on GSK-3 inhibition

Abed N. Azab; Julia F. Ishak; Jacob Kaplanski; Vered Delbar; Miriam L. Greenberg

doi:10.2217/14796708.3.4.433

Mechanisms of action of the mood stabilizer valproate: A focus on GSK-3 inhibition

Abed N. Azab, Julia F. Ishak, Jacob Kaplanski, Vered Delbar, Miriam L. Greenberg

Research output: Contribution to journal › Review article › peer-review

6 Scopus citations

Abstract

Valproate is the most widely prescribed antiepileptic drug worldwide, and it is also used in the treatment of bipolar affective disorder, migraine headache and cancer. However, the therapeutic mechanism of action of valproate in these illness states is not understood. This article reviews the pharmacological effects of valproate that may explain its therapeutic efficacy. It focuses on the hypothesis that inhibition of glycogen synthase kinase-3 by valproate is a crucial therapeutic mechanism of this drug in the treatment of bipolar affective disorder. Other cellular pathways and signaling molecules that are targets of valproate (such as inositol de novo blosynthesis, histone deacetylase, protein kinase C, γ-aminobutyric acid, the extracellular signal-regulated kinase pathway and others) are also discussed.

Original language	English
Pages (from-to)	433-445
Number of pages	13
Journal	Future Neurology
Volume	3
Issue number	4
DOIs	https://doi.org/10.2217/14796708.3.4.433
State	Published - 1 Jul 2008

Keywords

Bipolar disorder
Extracellular signal-regulated kinase
GABA
Glycogen synthase kinase-3
Histone deacetylase
Inositol
Lithium
PKC
Valproic acid

ASJC Scopus subject areas

Neurology
Clinical Neurology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2217/14796708.3.4.433

Cite this

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title = "Mechanisms of action of the mood stabilizer valproate: A focus on GSK-3 inhibition",

abstract = "Valproate is the most widely prescribed antiepileptic drug worldwide, and it is also used in the treatment of bipolar affective disorder, migraine headache and cancer. However, the therapeutic mechanism of action of valproate in these illness states is not understood. This article reviews the pharmacological effects of valproate that may explain its therapeutic efficacy. It focuses on the hypothesis that inhibition of glycogen synthase kinase-3 by valproate is a crucial therapeutic mechanism of this drug in the treatment of bipolar affective disorder. Other cellular pathways and signaling molecules that are targets of valproate (such as inositol de novo blosynthesis, histone deacetylase, protein kinase C, γ-aminobutyric acid, the extracellular signal-regulated kinase pathway and others) are also discussed.",

keywords = "Bipolar disorder, Extracellular signal-regulated kinase, GABA, Glycogen synthase kinase-3, Histone deacetylase, Inositol, Lithium, PKC, Valproic acid",

author = "Azab, {Abed N.} and Ishak, {Julia F.} and Jacob Kaplanski and Vered Delbar and Greenberg, {Miriam L.}",

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T2 - A focus on GSK-3 inhibition

AU - Azab, Abed N.

AU - Ishak, Julia F.

AU - Kaplanski, Jacob

AU - Delbar, Vered

AU - Greenberg, Miriam L.

PY - 2008/7/1

Y1 - 2008/7/1

N2 - Valproate is the most widely prescribed antiepileptic drug worldwide, and it is also used in the treatment of bipolar affective disorder, migraine headache and cancer. However, the therapeutic mechanism of action of valproate in these illness states is not understood. This article reviews the pharmacological effects of valproate that may explain its therapeutic efficacy. It focuses on the hypothesis that inhibition of glycogen synthase kinase-3 by valproate is a crucial therapeutic mechanism of this drug in the treatment of bipolar affective disorder. Other cellular pathways and signaling molecules that are targets of valproate (such as inositol de novo blosynthesis, histone deacetylase, protein kinase C, γ-aminobutyric acid, the extracellular signal-regulated kinase pathway and others) are also discussed.

AB - Valproate is the most widely prescribed antiepileptic drug worldwide, and it is also used in the treatment of bipolar affective disorder, migraine headache and cancer. However, the therapeutic mechanism of action of valproate in these illness states is not understood. This article reviews the pharmacological effects of valproate that may explain its therapeutic efficacy. It focuses on the hypothesis that inhibition of glycogen synthase kinase-3 by valproate is a crucial therapeutic mechanism of this drug in the treatment of bipolar affective disorder. Other cellular pathways and signaling molecules that are targets of valproate (such as inositol de novo blosynthesis, histone deacetylase, protein kinase C, γ-aminobutyric acid, the extracellular signal-regulated kinase pathway and others) are also discussed.

KW - Bipolar disorder

KW - Extracellular signal-regulated kinase

KW - GABA

KW - Glycogen synthase kinase-3

KW - Histone deacetylase

KW - Inositol

KW - Lithium

KW - PKC

KW - Valproic acid

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DO - 10.2217/14796708.3.4.433

M3 - Review article

AN - SCOPUS:47249146018

SN - 1479-6708

VL - 3

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JO - Future Neurology

JF - Future Neurology

IS - 4

ER -

Mechanisms of action of the mood stabilizer valproate: A focus on GSK-3 inhibition

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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