Valproate and GABAergic System Effects

Winterer, Georg

doi:10.1038/sj.npp.1300245

Cited by 10 publications

(7 citation statements)

References 16 publications

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“…Fetter-Pruneda et al (2013), nonetheless, first ruled out this long held presumption, and then advanced the hypothesis that S1 expansion rapidly progresses during the first days of life following enucleation after the precocious specification of the S1 and the overgrowth of the somatosensory thalamo-cortical afferents (STCAs). In addition, Fetter-Pruneda et al (2013) revealed that S1 expansion in BE rats is prevented after administering valproic acid, a fatty acid that seems to dampen the activity voltage-gated sodium channels (McLean and Macdonald, 1986; Zona and Avoli, 1990), promotes GABAergic neuronal differentiation (Laeng et al, 2004), increases GABA levels [(Löscher, 1993; Sawaya et al, 1975); although see (Winterer, 2003)] and inhibits histone deacetylases activity (Phiel et al, 2001). In conjunction, these observations suggest that epigenetic mechanisms governing the timing of S1 specification and the rate and pattern of STCAs growth, likely by shifting patterns of spontaneous activity and local GABAergic function, might explain S1 expansion in enucleated rats.…”

Section: Introductionmentioning

confidence: 99%

Bilateral enucleation at birth modifies calcium spike amplitude, but not frequency, in neurons of the somatosensory thalamus and cortex: Implications for developmental cross-modal plasticity

et al. 2019

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Section: Introductionmentioning

confidence: 99%

Bilateral enucleation at birth modifies calcium spike amplitude, but not frequency, in neurons of the somatosensory thalamus and cortex: Implications for developmental cross-modal plasticity

et al. 2019

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“…Indeed, there exists concern that many of the studies on GABA levels have utilized supra therapeutic levels of VPA, which is suggestive of other effects of VPA on the above-mentioned enzymes as being more relevant. 121 Histone deacetylase Histones are components of nucleosomes, on which DNA is bound to form chromatin (Figure 2). Acetylation of histones reduces their affinity for DNA and is a major epigenetic regulator of gene expression.…”

Section: Direct Targets Of Valproatementioning

confidence: 99%

Emerging experimental therapeutics for bipolar disorder: insights from the molecular and cellular actions of current mood stabilizers

et al. 2004

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Bipolar disorder afflicts approximately 1-3% of both men and women, and is coincident with major economic, societal, medical, and interpersonal consequences. Current mediations used for its treatment are associated with variable rates of efficacy and often intolerable side effects. While preclinical and clinical knowledge in the neurosciences has expanded at a tremendous rate, recent years have seen no major breakthroughs in the development of novel types of treatment for bipolar disorder. We review here approaches to develop novel treatments specifically for bipolar disorder. Deliberate (ie not by serendipity) treatments may come from one of two general mechanisms: (1) Understanding the mechanism of action of current medications and thereafter designing novel drugs that mimics these mechanism(s); (2) Basing medication development upon the hypothetical or proven underlying pathophysiology of bipolar disorder. In this review, we focus upon the first approach. Molecular and cellular targets of current mood stabilizers include lithium inhibitable enzymes where lithium competes for a magnesium binding site (inositol monophosphatase, inositol polyphosphate 1-phosphatase, glycogen synthase kinase-3 (GSK-3), fructose 1,6-bisphosphatase, bisphosphate nucleotidase, phosphoglucomutase), valproate inhibitable enzymes (succinate semialdehyde dehydrogenase, succinate semialdehyde reductase, histone deacetylase), targets of carbamazepine (sodium channels, adenosine receptors, adenylate cyclase), and signaling pathways regulated by multiple drugs of different classes (phosphoinositol/protein kinase C, cyclic AMP, arachidonic acid, neurotrophic pathways). While the task of developing novel medications for bipolar disorder is truly daunting, we are hopeful that understanding the mechanism of action of current mood stabilizers will ultimately lead clinical trials with more specific medications and thus better treatments those who suffer from this devastating illness.

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“…Dr Winterer's letter (Winterer, 2003) disagreed. Herein, we present two cases that support that VPA works through dopaminergic mechanisms.…”

Section: Sirmentioning

confidence: 98%

Valproic Acid Induces Manifestations of Simultaneous Dopamine Enhancement and Reduction in Schizophrenia

López¹,

Wassef²,

Molloy³

et al. 2004

Neuropsychopharmacol

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Valproate and GABAergic System Effects

Cited by 10 publications

References 16 publications

Bilateral enucleation at birth modifies calcium spike amplitude, but not frequency, in neurons of the somatosensory thalamus and cortex: Implications for developmental cross-modal plasticity

Bilateral enucleation at birth modifies calcium spike amplitude, but not frequency, in neurons of the somatosensory thalamus and cortex: Implications for developmental cross-modal plasticity

Emerging experimental therapeutics for bipolar disorder: insights from the molecular and cellular actions of current mood stabilizers

Valproic Acid Induces Manifestations of Simultaneous Dopamine Enhancement and Reduction in Schizophrenia

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