The acute effect of valproate on cerebral energy metabolism in mice

Johannessen, Cecilie U.; Petersen, Dirk; Fonnum, Frode; Hassel, Bjørnar

doi:10.1016/s0920-1211(01)00308-4

Cited by 30 publications

(28 citation statements)

References 39 publications

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“…In vitro VPA has been shown to inhibit GABA transaminase, succinic semialdehyde dehydrogenase, and á-ketoglutarate dehydrogenase (44,77,118). Consequently brain levels of GABA tend to increase acutely (9,21,62). As discussed by Löscher (80), GABA turnover is elevated in certain brain areas which are important in seizure inititation and propagation, such as the substantia nigra.…”

Section: Effects Of Vpa On Gaba and Inhibitory Neurotransmissionmentioning

confidence: 97%

“…As demonstrated by 13 C nuclear magnetic resonance (NMR) spectroscopy in mice, the synthesis of glutamate is reduced after acute administration of VPA, which could lead to a decrease in glutamatergic neurotransmission (62). This decrease is accompanied by an increase in the synthesis of GABA (62).…”

Section: Effects Of Vpa On Excitatory Neurotransmissionmentioning

confidence: 99%

“…This decrease is accompanied by an increase in the synthesis of GABA (62). This effect seems to be potentially advantageous, since it will reduce excitability and will reestablish a balance between the excitatory amino acid neurotransmitter glutamate and the inhibitory amino acid neurotransmitter GABA.…”

Section: Effects Of Vpa On Excitatory Neurotransmissionmentioning

confidence: 99%

“…Acutely, VPA decreases aspartate levels in whole rodent brain (21,62). The role of aspartate as a candidate excitatory neurotransmitter has recently been discussed.…”

Section: Effects Of Vpa On Excitatory Neurotransmissionmentioning

confidence: 99%

“…Chronic treatment with VPA has been postulated to upregulate cell surface expression of sodium channels (123). However, the importance of inhibition of voltage-gated sodium channels as an independent mechanism of action of VPA has been lately questioned (2,62,79,81). Löscher (81) concluded, that there is no convincing evidence that at therapeutically relevant concentrations VPA blocks voltage-dependent sodium currents.…”

Section: Effects Of Vpa On Ion Channelsmentioning

confidence: 99%

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Valproate: Past, Present, and Future

2003

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Preclinical studies have been carried out during the past four decades to investigate the different mechanisms of action of valproate (VPA). The mechanisms of VPA which seem to be of clinical importance include increased GABAergic activity, reduction in excitatory neurotransmission, and modification of monoamines. These mechanisms are discussed in relation to the various clinical uses of the drug. VPA is widely used as an antiepileptic drug with a broad spectrum of activity. In patients, VPA possesses efficacy in the treatment of various epileptic seizures such as absence, myoclonic, and generalized tonicclonic seizures. It is also effective in the treatment of partial seizures with or without secondary generalization and acutely in status epilepticus.The pharmacokinetic aspects of VPA and the frequent drug interactions between VPA and other drugs are discussed. The available methods for the determination of VPA in body fluids are briefly evaluated.At present, investigations and clinical trials are carried out and evaluated to explore the new indications for VPA in other conditions such as in psychiatric disorders, migraine and neuropathic pain. Furthermore, the toxicity of VPA, both regarding commonly occurring side effects and potential idiosyncratic reactions are described. Derivatives of VPA with improved efficacy and tolerability are in development.

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Section: Effects Of Vpa On Gaba and Inhibitory Neurotransmissionmentioning

confidence: 97%

Section: Effects Of Vpa On Excitatory Neurotransmissionmentioning

confidence: 99%

Section: Effects Of Vpa On Excitatory Neurotransmissionmentioning

confidence: 99%

“…Acutely, VPA decreases aspartate levels in whole rodent brain (21,62). The role of aspartate as a candidate excitatory neurotransmitter has recently been discussed.…”

Section: Effects Of Vpa On Excitatory Neurotransmissionmentioning

confidence: 99%

Section: Effects Of Vpa On Ion Channelsmentioning

confidence: 99%

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Valproate: Past, Present, and Future

2003

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Chronic treatment with both lithium and sodium valproate may normalize phosphoinositol cycle activity in bipolar patients

Silverstone

O'Donnell

et al. 2002

Human Psychopharmacology

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Sodium valproate inhibits glucose transport and exacerbates Glut1‐deficiency in vitro

Wong

Chu

Lai

et al. 2005

J of Cellular Biochemistry

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Anticonvulsant sodium valproate interferes with brain glucose metabolism. The mechanism underlying such metabolic disturbance is unclear. We tested the hypothesis that sodium valproate interferes with cellular glucose transport with a focus on Glut1 since glucose transport across the blood-brain barrier relies on this transporter. Cell types enriched with Glut1 expression including human erythrocytes, human skin fibroblasts, and rat astrocytes were used to study the effects of sodium valproate on glucose transport. Sodium valproate significantly inhibited Glut1 activity in normal and Glut1-deficient erythrocytes by 20%-30%, causing a corresponding reduction of Vmax of glucose transport. Similarly, in primary astrocytes as well as in normal and Glut1-deficient fibroblasts, sodium valproate inhibited glucose transport by 20%-40% (P < 0.05), accompanied by an up to 60% downregulation of GLUT1 mRNA expression (P < 0.05). In conclusion, sodium valproate inhibits glucose transport and exacerbates Glut1 deficiency in vitro. Our findings imply the importance of prudent use of sodium valproate for patients with compromised Glut1 function.

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The acute effect of valproate on cerebral energy metabolism in mice

Cited by 30 publications

References 39 publications

Valproate: Past, Present, and Future

Valproate: Past, Present, and Future

Chronic treatment with both lithium and sodium valproate may normalize phosphoinositol cycle activity in bipolar patients

Sodium valproate inhibits glucose transport and exacerbates Glut1‐deficiency in vitro

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