Mechanism of anticonvulsant action of valproate

Chapman, A. Chaston; Keane, P.E.; Meldrum, Brian S.; Simiand, Jacques; Vernières, Jean-Claude

doi:10.1016/0301-0082(82)90010-7

Cited by 338 publications

(150 citation statements)

References 192 publications

Supporting

Mentioning

144

Contrasting

Unclassified

Order By: Relevance

“…It has also been reported that the co-administration of lamotrigine and valproic acid reduced total lamotrigine clearance, whereas the renal clearance of lamotrigine remained unchanged. 26,27) In addition, the plasma elimination half-life and area under the curve of lamotrigine were increased. These alterations in the pharmacokinetics of lamotrigine were attributed to impaired glucuronide formation in the liver due to the competitive inhibition of hepatic enzymes by valproic acid.…”

Section: Discussionmentioning

confidence: 99%

Correlation between the Efficacy of Lamotrigine and the Serum Lamotrigine Level during the Remission Phase of Acute Bipolar II Depression: A Naturalistic and Unblinded Prospective Pilot Study

Kikkawa

Kitamura

Aiba

et al. 2017

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Lamotrigine has acute antidepressant effects in patients with bipolar disorder. However, there is little information regarding appropriate serum levels of lamotrigine and the time until remission after the start of lamotrigine therapy in patients with bipolar II depression. This was a naturalistic and unblinded prospective pilot study. Twelve patients' depressive symptoms were evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS) at the start of treatment and at the time of remission, and blood samples were obtained at the time of remission. Mahalanobis distance was used to analyze the relationship between the MADRS improvement rate and the serum lamotrigine level. Furthermore, we calculated the Spearman's rank correlation coefficient for the relationship between the MADRS improvement rate and the serum lamotrigine level, and produced box plots of the serum lamotrigine level at remission and the time until remission. The Mahalanobis distance for the patient that was co-administered lamotrigine and valproic acid differed significantly from those of the other patients (p<0.001). There was no linear relationship between the serum lamotrigine level and the MADRS improvement rate among the patients that did not receive valproic acid. The median time from the start of lamotrigine therapy until remission was 6 weeks. The serum lamotrigine level does not have an important impact on the acute therapeutic effects of lamotrigine on bipolar II depression. In addition, we consider that different treatment options should be considered for non-responders who do not exhibit any improvement after the administration of lamotrigine for approximately 6 weeks.

show abstract

Section: Discussionmentioning

confidence: 99%

Correlation between the Efficacy of Lamotrigine and the Serum Lamotrigine Level during the Remission Phase of Acute Bipolar II Depression: A Naturalistic and Unblinded Prospective Pilot Study

Kikkawa

Kitamura

Aiba

et al. 2017

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…19 Malformations of cortical development, including polymicrogyria, are an important cause of therapy-resistant epilepsy. 20,21 In patient 1, epilepsy is associated with polymicrogyria, which might explain the therapy resistant nature of the observed epilepsy in this patient.…”

Section: Discussionmentioning

confidence: 99%

Genomic aberrations of the CACNA2D1 gene in three patients with epilepsy and intellectual disability

et al. 2014

View full text Add to dashboard Cite

Voltage-gated calcium channels have an important role in neurotransmission. Aberrations affecting genes encoding the alpha subunit of these channels have been associated with epilepsy and neuropsychiatric disorders such as autism or schizophrenia. Here we report three patients with a genomic aberration affecting the CACNA2D1 gene encoding the alpha 2 delta subunit of these voltage-gated calcium channels. All three patients present with epilepsy and intellectual disability pinpointing the CACNA2D1 gene as an interesting candidate gene for these clinical features. Besides these characteristics, patient 2 also presents with obesity with hyperinsulinism, which is very likely to be caused by deletion of the CD36 gene

show abstract

“…chemotherapy, and/or radiotherapy. Furthermore, VPA has convenient pharmacokinetic properties with a significantly longer biological half-life than the other HDACIs (39).…”

Section: Discussionmentioning

confidence: 99%

Histone Deacetylase Inhibitors Have a Profound Antigrowth Activity in Endometrial Cancer Cells

Takai

Desmond

Kumagai

et al. 2004

Clinical Cancer Research

218

156

View full text Add to dashboard Cite

Purpose: HDAC inhibitors (HDACIs) have been shown to inhibit cancer cell proliferation, stimulate apoptosis, and induce cell cycle arrest. Our purpose was to investigate the antiproliferative effects of the HDACIs [suberoyl anilide bishydroxamine, valproic acid (VPA), trichostatin A, and sodium butyrate] against six endometrial cancer cell lines.Experimental Design: Endometrial cancer cells were treated with a variety of HDACIs, and the effect on cell growth, cell cycle, and apoptosis was measured. The ability of VPA to inhibit the growth of endometrial tumors growing in immunodeficient mice was also assessed.Results: Clonogenic assays showed that all cancer cell lines were sensitive to the growth inhibitory effect of HDACIs. Cell cycle analysis indicated that treatment with HDACIs decreased the proportion of cells in S phase and increased the proportion of cells in the G 0 -G 1 and/or G 2 -M phases of the cell cycle. Terminal deoxynucleotidyl transferase-mediated nick end labeling assays showed that HDACIs induced apoptosis. This was concomitant with altered expression of genes related to malignant phenotype, including an increase in p21 Waf1 , p27 Kip7 , and E-cadherin and a decrease in Bcl-2 and cyclin-D1 and -D2. Chromatin immunoprecipitation analysis revealed a remarkable increase in levels of acetylated histones associated with the p21 promoter after suberoyl anilide bishydroxamine treatment. In nude mice experiments, VPA inhibited significantly human uterine tumor growth without toxic side effects.Conclusions: These results suggest that HDACIs are effective in inhibiting growth of endometrial cancer cells in vitro and in nude mice, without toxic side effects. The findings raise the possibility that HDACIs may prove particularly effective in treatment of endometrial cancers.

show abstract

Mechanism of anticonvulsant action of valproate

Cited by 338 publications

References 192 publications

Correlation between the Efficacy of Lamotrigine and the Serum Lamotrigine Level during the Remission Phase of Acute Bipolar II Depression: A Naturalistic and Unblinded Prospective Pilot Study

Correlation between the Efficacy of Lamotrigine and the Serum Lamotrigine Level during the Remission Phase of Acute Bipolar II Depression: A Naturalistic and Unblinded Prospective Pilot Study

Genomic aberrations of the CACNA2D1 gene in three patients with epilepsy and intellectual disability

Histone Deacetylase Inhibitors Have a Profound Antigrowth Activity in Endometrial Cancer Cells

Contact Info

Product

Resources

About