Tetramethylcyclopropyl analogue of the leading antiepileptic drug, valproic acid: Evaluation of the teratogenic effects of its amide derivatives in NMRI mice

2008 ◽  
Vol 82 (9) ◽  
pp. 610-621 ◽  
Author(s):  
Akinobu Okada ◽  
Yuko Onishi ◽  
Boris Yagen ◽  
Jakob Avi Shimshoni ◽  
Dan Kaufmann ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Antiepileptic Drug ◽  
Teratogenic Effects ◽  
Nmri Mice ◽  
Amide Derivatives

Valproic Acid:

1999 ◽  
Vol 16 (2) ◽  
pp. 130-136 ◽  
Author(s):  
Sayonara Beatriz Ranciaro Fagundes
Keyword(s):  
Health Care ◽  
Valproic Acid ◽  
Antiepileptic Drug ◽  
Detailed Analysis ◽  
Side Effect ◽  
Side Effect Profile ◽  
Care Givers

Clinical pharmacologists, neurologists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug when determining which drug is best for a given patient.The purpose of this study was to investigate valproic acid with a detailed analysis of the different reports.

scholarly journals Preliminary Results Regarding Sleep in a Zebrafish Model of Autism Spectrum Disorder

2021 ◽  
Vol 11 (5) ◽  
pp. 556
Author(s):  
Madalina Andreea Robea ◽  
Alin Ciobica ◽  
Alexandrina-Stefania Curpan ◽  
Gabriel Plavan ◽  
Stefan Strungaru ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Valproic Acid ◽  
Social Behavior ◽  
Antiepileptic Drug ◽  
Alternative Model ◽  
Neurological Diseases ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Zebrafish Model ◽  
Developmental Defects

Autism spectrum disorder (ASD) is one of the most salient developmental neurological diseases and remarkable similarities have been found between humans and model animals of ASD. A common method of inducing ASD in zebrafish is by administrating valproic acid (VPA), which is an antiepileptic drug that is strongly linked with developmental defects in children. In the present study we replicated and extended the findings of VPA on social behavior in zebrafish by adding several sleep observations. Juvenile zebrafish manifested hyperactivity and an increase in ASD-like social behaviors but, interestingly, only exhibited minimal alterations in sleep. Our study confirmed that VPA can generate specific ASD symptoms, indicating that the zebrafish is an alternative model in this field of research.

scholarly journals The Impact of Chlorambucil and Valproic Acid on Cell Viability, Apoptosis and Expression of p21, HDM2, BCL2 and MCL1 Genes in Chronic Lymphocytic Leukemia

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1088
Author(s):  
Katarzyna Lipska ◽  
Agata Filip ◽  
Anna Gumieniczek
Keyword(s):  
Valproic Acid ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Viability ◽  
Antiepileptic Drug ◽  
Drug Combination ◽  
Target Genes ◽  
Histone Deacetylation ◽  
Lymphocytic Leukemia ◽  
Malignant Cells ◽  
The Impact

Malignant cells in chronic lymphocytic leukemia (CLL) show resistance to apoptosis, as well as to chemotherapy, which are related to deletions or mutations of TP53, high expression of MCL1 and BCL2 genes and other abnormalities. Thus, the main goal of the present study was to assess the impact of chlorambucil (CLB) combined with valproic acid (VPA), a known antiepileptic drug and histone deacetylation inhibitor, on apoptosis of the cells isolated from 17 patients with CLL. After incubation with CLB (17.5 µM) and VPA (0.5 mM), percentage of apoptosis, as well as expression of two TP53 target genes (p21 and HDM2) and two genes from Bcl-2 family (BCL2 and MCL1), were tested. As a result, an increased percentage of apoptosis was observed for CLL cells treated with CLB and VPA, and with CLB alone. Under the treatment with the drug combination, the expression of p21 gene was visibly higher than under the treatment with CLB alone. At the same time, the cultures under CLB treatment showed visibly higher expression of BCL2 than the cultures with VPA alone. Thus, the present study strongly suggests further investigations on the CLB and VPA combination in CLL treatment.

scholarly journals Pharmacological modulation of cell functional activity with valproic acid and erythropoietin

2019 ◽  
Vol 5 (2) ◽  
pp. 89-99
Author(s):  
Polina A. Golubinskaya ◽  
Marina V. Sarycheva ◽  
Svetlana Y. Burda ◽  
Maksim V. Puzanov ◽  
Natalya A. Nadezhdina ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Antiepileptic Drug ◽  
Axial Skeleton ◽  
Pharmacological Modulation ◽  
Inhibition Of Growth ◽  
Acid Effect ◽  
Branched Chain ◽  
Growth Of Tumor

Introduction: Valproic acid (VA) is carboxylic acid with a branched chain, which is used as an antiepileptic drug. Valproic acid influence on cells in vivo: VA, which is an antiepileptic drug, is also a teratogen, which causes defects of a neural tube and an axial skeleton, although the mechanisms are not yet fully clear. Valproic acid influence on mesenchymal stem cells (MSC) in vitro: It is shown that valproic acid reduces the intracellular level of oxygen active forms. Valproic acid effect on tumor cells: VA inhibits tumor growth through several mechanisms, including the cell cycle stop, differentiation induction and inhibition of growth of tumor vessels. Valproic acid influence on enzymes: It affects mainly GSK-3. Valproic acid influence on animals’ cells: It is shown that VA can significantly improve an ability to develop in vitro and improve nuclear reprogramming of embryos. Erythropoietin (EPO): Is an hypoxia-induced hormone and a cytokine, which is necessary for normal erythropoiesis. EPO is widely used in in vitro experiments. Conclusion: Thus, the influence of VA and EPO on cells can be used in cell technologies.

scholarly journals Evaluation of Teratogenic Activity of Antiepileptic Drug Lamotrigine in Mouse Fetuses

Folia Medica ◽  
2019 ◽  
Vol 61 (1) ◽  
pp. 84-89
Author(s):  
Gholam Reza Mobini ◽  
Abbas Karimi ◽  
Abolfazl Akbari ◽  
Forouzan Rahmani
Keyword(s):  
Risk Factor ◽  
Antiepileptic Drug ◽  
Congenital Abnormalities ◽  
Newborn Infants ◽  
Treatment Protocol ◽  
Teratogenic Effects ◽  
Increased Risk ◽  
Pregnant Mice ◽  
Mock Treatment ◽  
Mouse Fetuses

Abstract Background: Use of antiepileptic drugs during pregnancy can be associated with an increased risk of teratogenicity as well as congenital abnormalities. However, there are numerous discrepancies to determine whether lamotrigine, as an antiepileptic drug, can significantly induce malformation in newborn infants or not. Thus, the purpose of the study was to evaluate the teratogenic effects of lamotrigine on mouse fetuses. Materials and methods: In the present study, 21 pregnant mice were assigned to four groups. Groups 1 and 2 (controls) received mock treatment and ethanol 20%, respectively. Groups 3 and 4 (treatment) were intraperitoneally administered with 25 and 75 mg/kg lamotrigine for three days, respectively. The treatment protocol was performed within the gestational days of 9-18 in all groups. On gestational day 18, 117 fetuses were taken out of the fallopian tube of studied mice and then examined for any anomalies (vertebral, limbs and cranial), followed by a measurement of their height and weight. Results: The results revealed that, in the treated groups, the weight and the height had significantly decreased (p<0.01) and also various anomalies were evident. Moreover, as the dose of lamotrigine increased, the decrease in the weight and the height and rising trend in anomalies were intensified. Conclusion: According to the findings, lamotrigine (LTG) could be considered as a risk factor for the development of the anomalies examined.

Valproic Acid: A Different View

PEDIATRICS ◽  
1982 ◽  
Vol 70 (2) ◽  
pp. 331-331
Author(s):  
J. Kiffin Penry
Keyword(s):  
Valproic Acid ◽  
Side Effects ◽  
American Academy ◽  
Antiepileptic Drug ◽  
Antiepileptic Drugs ◽  
Published Data ◽  
American Academy Of Pediatrics

The Committee on Drugs of the American Academy of Pediatrics has prepared a statement on the benefits and risks of the antiepileptic drug valproic acid; this statement appears in this issue of Pediatrics (70:316, 1982). This report is extensive and objective in its review of published data on valproic acid, and is of great value to practicing pediatricians for that reason. However, the review fails to place vaiproic acid in perspective with other marketed antiepileptic drugs, which in many instances have equally serious side effects.

Plasma homocysteine and aminothiol levels in idiopathic epilepsy patients receiving antiepileptic drugs

2019 ◽  
Vol 44 (5) ◽  
pp. 661-666
Author(s):  
Dilber Çoban Ramazan ◽  
Ülker Anadol ◽  
A. Destina Yalçın ◽  
A. Süha Yalçın
Keyword(s):  
Valproic Acid ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Antiepileptic Drug ◽  
Antiepileptic Drugs ◽  
Serum Vitamin ◽  
Idiopathic Epilepsy ◽  
Serum Folate ◽  
Significant Difference ◽  
Epileptic Patients

Abstract Objective Homocysteine is a sulfur containing amino acid that is formed during methionine metabolism. Patients under long-term antiepileptic drug treatment often have hyperhomocysteinemia. These patients have low levels of serum folate, vitamin B12 and vitamin B6, all of which are associated with homocysteine metabolism. We have investigated the effects of valproic acid and new generation antiepileptic drugs (lamotrigine and levetiracetam) on plasma levels of homocysteine and aminothiols as well as serum vitamin B12 and folic acid. Materials and methods Forty-seven idiopathic epileptic patients on antiepileptic drugs were compared with 38 age-matched healthy controls. Commercial immunoassay methods were used for vitamin B12 and folic acid analyses. Homocysteine, cysteine, cysteinylglycine and glutathione levels were determined by high performance liquid chromatography. Results There was no significant difference in patient and control values in terms of vitamin B12, folic acid and homocysteine. Valproic acid and lamotrigine seemed to effect aminothiol redox status. Glutathione levels of epileptic patients receiving valproic acid and lamotrigine were higher than controls. Conclusion Our results suggest that redox homeostasis may be impaired and glutathione synthesis increased in response to the oxidative stress caused by antiepileptic drug use.

scholarly journals The Effect of Piracetam on Valproic Acid Induced Congenital Malformations in Swiss Albino Mice

2019 ◽  
Vol 21 (3) ◽  
pp. 204-209
Author(s):  
Shamsher Shrestha ◽  
M. Singh ◽  
S.P. Mishra
Keyword(s):  
Valproic Acid ◽  
Brain Injuries ◽  
Treated Group ◽  
Aging Brain ◽  
Teratogenic Effects ◽  
Swiss Albino Mice ◽  
Group Iii ◽  
Group I ◽  
Albino Mice ◽  
Higher Doses

Valproic acid (VPA) is an antiepileptic drug which is widely used in humans and is a well known teratogenic agent when used during pregnancy. Piracetam is a nootropic or cognitive enhancer drug used to treat cognitive impairment in aging, brain injuries as well as dementia. In the present study, these two drugs VPA and Piracetam were administered orally to Swiss albino mice in the doses of400 mg/kg and 800 mg/kg body weight respectively from gestational day (GD) 6-11 in order to see the protective effect of Piracetam against VPA induced teratogenesis. The fetuses were collected on GD 18 after uterotomy and observed for gross malformations if any. In VPA treated group the malformations observed were exencephaly, cranioschisis, limb and tail defects, haemorrhage, resorptions and retardation. No such anomalies were observed in control and Piracetam treated groups. However,in VPA+ Piracetam treated group some resorptions and growth retardation were noted. This group showed highly significant (p < 0.001) protection against the teratogenic effects of VPA treated group though the developmental parameters were significantly reduced (p < 0.001) in comparison to those of group I (control) and group III (receiving piracetam). These findings suggest that Piracetam, if given in higher doses might protect the development in utero against the teratogenic effects of VPA.

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