-
Pharmacogenetics and Genomics Apr 2013
Topics: Cytochrome P-450 Enzyme System; Humans; Metabolic Networks and Pathways; Pharmacogenetics; Valproic Acid
PubMed: 23407051
DOI: 10.1097/FPC.0b013e32835ea0b2 -
Current Neuropharmacology 2023
Topics: Humans; Valproic Acid; Bipolar Disorder; Lithium; Antimanic Agents; Lithium Compounds
PubMed: 37203193
DOI: 10.2174/1570159X2104230307123319 -
Brazilian Journal of Biology = Revista... 2022Valproic acid in association with sodium valproate (VPA) is an important anticonvulsant drug used for decades to treat neurological disorders. VPA also acts as an... (Review)
Review
Valproic acid in association with sodium valproate (VPA) is an important anticonvulsant drug used for decades to treat neurological disorders. VPA also acts as an epigenetic modulator by inhibiting histone deacetylases, permitting histone acetylation, affecting the DNA and histone methylation status and gene expression, and inducing chromatin remodeling. Insects represent an important animal model for studies in several areas of science. Their high phenotypic plasticity makes them alternative models for epigenetic studies. This brief review emphasizes recent reports on insect epigenetics and the contribution of studies on the VPA action in insects, including effects on epigenetic markers, extending the pharmacological understanding of the potential of this drug, and demonstrating the usefulness of insects as an alternative animal model to drug studies.
Topics: Acetylation; Animals; Disease Models, Animal; Epigenesis, Genetic; Histones; Insecta; Valproic Acid
PubMed: 35416850
DOI: 10.1590/1519-6984.256045 -
Molecules (Basel, Switzerland) Dec 2021Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and... (Review)
Review
Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and neuropathic pain. Apart from this, VPA has potential therapeutic applications in other central nervous system (CNS) disorders and in various cancer types. Since the discovery of its anticonvulsant activity, substantial efforts have been made to develop structural analogues and derivatives in an attempt to increase potency and decrease adverse side effects, the most significant being teratogenicity and hepatotoxicity. Most of these compounds have shown reduced toxicity with improved potency. The simple structure of VPA offers a great advantage to its modification. This review briefly discusses the pharmacology and molecular targets of VPA. The article then elaborates on the structural modifications in VPA including amide-derivatives, acid and cyclic analogues, urea derivatives and pro-drugs, and compares their pharmacological profile with that of the parent molecule. The current challenges for the clinical use of these derivatives are also discussed. The review is expected to provide necessary knowledgebase for the further development of VPA-derived compounds.
Topics: Amides; Animals; Anticonvulsants; Drug Monitoring; Epilepsy; Humans; Molecular Structure; Structure-Activity Relationship; Teratogens; Urea; Valproic Acid
PubMed: 35011339
DOI: 10.3390/molecules27010104 -
Journal of Healthcare Engineering 2022Glioma is one of the most common intracranial tumors worldwide, and metastasis and chemoresistance remain a challenge in glioma treatment. This study aims to investigate...
Glioma is one of the most common intracranial tumors worldwide, and metastasis and chemoresistance remain a challenge in glioma treatment. This study aims to investigate the effect of sodium valproate on the invasion and metastasis of glioma cells and its mechanism. Glioma cell lines were stimulated with VPA at different concentrations and for different durations of action. U87 glioma cells were transfected with Smad4 plasmid and small interfering RNA, and the changes of EMT-related protein indexes in U87 cells after up- or downregulation of Smad4 were detected by Western blotting. Immunohistochemistry was used to detect the differences in the expression of Smad4, TIF1-, and TGF- proteins in 39 glioma clinical specimens from the Department of Pathology of our hospital. Based on the regulation of EMT-related transcription factors by VPA, our study indicates that VPA inhibits the EMT process of glioma by altering the expression level of Smad4, which is induced by TGF-1 to form a Smad3/4 complex, thus inducing the EMT process of the tumor and acting as an antitumor target to inhibit the invasive ability of glioma cells. Sodium valproate inhibits glioma invasion and metastasis through the regulation of Smad4 expression.
Topics: Brain Neoplasms; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Glioma; Humans; Valproic Acid
PubMed: 35251569
DOI: 10.1155/2022/4985781 -
The Cochrane Database of Systematic... Oct 2011Valproic acid and its sodium salt (sodium valproate) are antiepileptic drugs that are sometimes used to treat chronic neuropathic pain and fibromyalgia, although they... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Valproic acid and its sodium salt (sodium valproate) are antiepileptic drugs that are sometimes used to treat chronic neuropathic pain and fibromyalgia, although they are not licensed for this use.
OBJECTIVES
To evaluate the analgesic efficacy and adverse effects of valproic acid and sodium valproate in the management of chronic neuropathic pain and fibromyalgia.
SEARCH STRATEGY
We identified randomised controlled trials (RCTs) of valproic acid and sodium valproate in acute, and chronic pain by searching MEDLINE, EMBASE and Cochrane CENTRAL to June 2011, together with reference lists of retrieved papers and reviews.
SELECTION CRITERIA
RCTs that were double blind and of eight-weeks duration or longer, reporting on analgesic effects and adverse events with valproic acid and sodium valproate in the treatment of chronic neuropathic pain and fibromyalgia.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted results and scored for quality. We extracted efficacy and adverse event data, and examined issues of study quality.
MAIN RESULTS
We included three studies, two in diabetic neuropathy (42 participants treated with valproate, 42 with placebo), and one in post-herpetic neuralgia (23 treated with divalproex sodium, 22 with placebo). Study duration was eight or 12 weeks. No studies were found in fibromyalgia.Only one study reported one of our primary outcomes (≥ 50% pain relief), while all three reported group means for pain reduction from baseline to endpoint. In all three studies; efficacy results were given only for participants who completed the study. One study in diabetic neuropathy and the study in post-herpetic neuralgia reported significant differences between active and placebo groups, but there were insufficient data for reliable pooled analysis.More adverse events were reported with active treatment than placebo, and included nausea, drowsiness and abnormal liver function tests. One participant taking sodium valproate withdrew due to serious derangement of liver enzymes.
AUTHORS' CONCLUSIONS
These three studies no more than hint that sodium valproate may reduce pain in diabetic neuropathy, and divalproex sodium in post-herpetic neuralgia, but the use of 'completer' analysis may overestimate efficacy, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. There is insufficient evidence to support the use of valproic acid or sodium valproate as a first-line treatment for neuropathic pain. There is more robust evidence of greater efficacy for a small number of other drugs.
Topics: Adult; Analgesics; Diabetic Neuropathies; Fibromyalgia; Humans; Neuralgia, Postherpetic; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 21975791
DOI: 10.1002/14651858.CD009183.pub2 -
Viruses Nov 2020Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67%... (Review)
Review
Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67% of the global population under the age of 50 are infected with HSV-1 and 13% have clinically recurrent HSV-2 infections. The most prescribed antiherpetics are nucleoside analogues such as acyclovir, but the emergence of mutants resistant to these drugs and the lack of available vaccines against human HSVs has led to an imminent need for new antivirals. Valproic acid (VPA) is a branched short-chain fatty acid clinically used as a broad-spectrum antiepileptic drug in the treatment of neurological disorders, which has shown promising antiviral activity against some herpesviruses. Moreover, its amidic derivatives valpromide and valnoctamide also share this antiherpetic activity. This review summarizes the current research on the use of VPA and its amidic derivatives as alternatives to traditional antiherpetics in the fight against HSV infections.
Topics: Alphaherpesvirinae; Amides; Animals; Antiviral Agents; Dose-Response Relationship, Drug; Humans; Microbial Sensitivity Tests; Molecular Structure; Valproic Acid
PubMed: 33256172
DOI: 10.3390/v12121356 -
Revista Do Colegio Brasileiro de... 2022to recognize the effects of valproic acid (VPA), an epigenetic drug, on the bladder healing process, in rats.
PURPOSE
to recognize the effects of valproic acid (VPA), an epigenetic drug, on the bladder healing process, in rats.
METHOD
twenty male Wistar rats were divided in two groups: experimental (A), treated with VPA (150mg/Kg/day), and control (B) with 0.9% sodium chloridrate. Healing was analyzed on the third and seventh days, evaluating the inflammatory reaction, collagen synthesis and angiogenesis.
RESULTS
inflammatory reaction on the third day was minimal and acute in both groups. On the seventh day, it was subacute in both groups, moderate intensity in group A and minimal in group B (p=0.0476). Collagen III intensity, marked by immunohistochemistry, was similar in both groups. Collagen I intensity on the third day was similar in both groups, but on the seventh day it was higher in experimental than control (p=0.0476). Collagen evaluation by picrosiriusred allowed to verify that the presence of collagen III was similar in both groups (p=0.3312) on the third day, and it was higher in control on the seventh day (p=0.0015). Collagen I showed similarity on the third day (p=0.3100), and it was higher in control on the seventh day (p=0.0015). Vessel marked with anti-SMA counting showed fewer vessels on the third (p=0.0034) and seventh day (p=0.0087) in experimental group. The lower intensity of angiogenesis was confirmed with anti-CD34, on the third day (p=0,0006) and on the seventh day (p=0,0072).
CONCLUSION
VPA determined alterations in the bladder healing process, in rats, with lower collagen density and less angiogenic activity, but without compromising the integrity of the organ.
Topics: Male; Rats; Animals; Valproic Acid; Rats, Wistar; Urinary Bladder; Inflammation; Wound Healing
PubMed: 36449944
DOI: 10.1590/0100-6991e-20223399-en -
Clinical Medicine (London, England) Apr 2018Antiepileptic medications, and valproate principally, are commonly prescribed teratogens. There is significant concern that we are not doing enough to educate clinicians... (Review)
Review
Antiepileptic medications, and valproate principally, are commonly prescribed teratogens. There is significant concern that we are not doing enough to educate clinicians and potential parents about the risks of valproate in pregnancy. There is clear advice from the Medicines and Healthcare products Regulatory Agency and the International League Against Epilepsy about the risks of valproate exposure Reviews and guidelines that are focused on fetal risk, however, fall short in being able to fully replicate the complexity of a real clinical decision. Valproate is certainly life-changing if your child is one of the 10% with a major malformation or 30-40% with a neurodevelopmental disorder, but valproate is also potentially life-saving in the context of ensuring the best possible seizure control for some mothers with epilepsy. There are significant knowledge gaps regarding the risks to mothers who elect to take another drug, or to mother and baby if she comes off medication entirely. We also should be doing more to reduce rates of sudden unexpected death in epilepsy (SUDEP), which is recognised as a key target when evaluating all maternal deaths.
Topics: Anticonvulsants; England; Epilepsy; Female; Humans; Maternal Exposure; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prescriptions; Teratogens; Treatment Outcome; Valproic Acid
PubMed: 29700085
DOI: 10.7861/clinmedicine.18-2-s1 -
The Journal of Applied Laboratory... Apr 2021Valproic acid (VPA) is a broad-spectrum anticonvulsant drug. Under normal conditions, this drug is highly protein bound. However, in patients with hypoalbuminemia, the...
BACKGROUND
Valproic acid (VPA) is a broad-spectrum anticonvulsant drug. Under normal conditions, this drug is highly protein bound. However, in patients with hypoalbuminemia, the free fraction can increase substantially while the total VPA levels remain in therapeutic range. The neurologic activity and toxicity of the drug are directly related to free drug levels.
METHODS
Our in-house free VPA assay was validated using 20 patient samples obtained from a reference laboratory (RL1). It was further evaluated by parallel testing with RL1 using samples collected from our patients. Subsequently, sample handling effects were investigated by comparing free VPA levels measured in our laboratory to 3 selected RLs with different sample transportation conditions.
RESULTS
No significant bias was observed between the in-house assay (y) and RL1 (x) assay in free VPA measurement (y = 1.12x + 0.072, r = 0.994). However, patient samples collected in our institution and sent to RL1 revealed significant negative bias (y = 0.776x - 3.861, r = 0.954). A large discrepancy in free VPA levels was further observed from identical aliquots of the same samples transported to 3 RLs in different conditions.
CONCLUSIONS
Our study demonstrated that sample handling has significant impact on free VPA levels. The observed magnitude of variation exceeds a clinically acceptable limit and could alter clinical decisions.
Topics: Anticonvulsants; Humans; Specimen Handling; Valproic Acid
PubMed: 33249432
DOI: 10.1093/jalm/jfaa181