Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: KEGG:D00710 (Sodium valproate)
320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Headache-prone patients have many highly effective therapeutic options open to them. Used only at the time of headache, sumatriptan succinate by mouth or injection and dihydroergotamine nasal spray are novel choices now or soon to be available. The original migraine therapy, ergotamine, is highly effective in its rectal suppository formulation, when used at a subnauseating dosage. Valproate sodium is the latest addition to the many therapies available for long-term stabilization.
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PMID:Headache. 797 70

We studied vestibulo-ocular reflex measurements in a group of 12 patients suffering from migraine without aura and evaluated the effect of sodium valproate given as prophylactic migraine therapy. The study was randomized, double blind and placebo controlled, with a crossover design. The horizontal vestibulo-ocular reflex was evaluated by the Sinusoidal Harmonic Acceleration test at 0.01, 0.02, 0.04, 0.08 and 0.16 Hz using a computerized rotatory chair system. No abnormalities were found for the vestibulo-ocular reflex gain, phase and asymmetry at each of the frequencies examined during the placebo treatment. These normal vestibulo-ocular reflex measurements contrasted with the repeated complaints of dizziness, vertigo and unsteadiness reported by 7 patients (58%). Sodium valproate affected neither vestibulo-ocular responses nor vestibular complaints but was effective in reducing migraine attacks in 8 of the 12 patients. These results demonstrate that the low frequency vestibulo-ocular reflex measurements are normal in patients suffering from migraine without aura.
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PMID:Vestibulo-ocular reflex in migraine patients: the effect of sodium valproate. 848 8

Recent studies of the visual cortex in patients with migraine have generally concluded that migraine (particularly migraine with aura) is associated with a state of functional cortical hyperexcitability. The mechanisms giving rise to this hyperexcitability have hitherto been unclear. This paper reports two studies that used a novel investigative technique, derived from basic research in vision science, to examine specific deficits of inhibitory processing in primary visual cortex. The technique is termed the metacontrast test, and it examines visual masking under highly specified conditions. In Study 1, 12 migraine with aura patients (MA), 12 age-matched migraine without aura patients (MO) and 12 age- and sex-matched headache-free control subjects (C) were compared using the metacontrast test. MA patients were significantly less susceptible to visual masking in the metacontrast test than both MO and C groups: this result is highly consistent with a deficit in cortical inhibitory processing in MA patients. Study 2 examined MA patients taking a variety of migraine prophylactics, again using the metacontrast test. Test results normalized in those MA patients taking sodium valproate, but not in those taking other prophylactics. Sodium valproate is a GABA-A agonist that is known to cross the blood-brain barrier: GABA-ergic networks act as the primary inhibitory mechanism in visual cortex. Taken together, the results of these studies argue that cortical hyperexcitability, at least in MA patients, is likely to be a result of deficient intracortical inhibitory processes.
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PMID:Cortical hyperexcitability is cortical under-inhibition: evidence from a novel functional test of migraine patients. 1107 34

The mainstay of migraine treatment is pharmacotherapy. There have been numerous medications used to prevent migraine headaches, including b-blockers, calcium-channel blockers, anticonvulsants, and nonsteroidal anti-inflammatory drugs. Sodium valproate is the only antiepileptic drug approved by the Food and Drug Administration for migraine prevention. Newer antiepileptics, including gabapentin and topiramate, are being evaluated for their role in preventive therapy. The mechanism of action of antiepileptics is not fully understood, but they all share a common role in enhancing gamma-aminobutyric acid-mediated inhibition. This article reviews the role of anticonvulsants in preventive migraine therapy.
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PMID:The role of anticonvulsants in preventive migraine therapy. 1252 73

Several trials have asserted that some anticonvulsant drugs seem to be useful for the prophylaxis of migraine, but systematic reviews are sparse. We independently searched PubMed, EMBASE and the Cochrane Central Register of Controlled Trials until 2005, as well as Headache and Cephalalgia through April 2006, for prospective, controlled trials of anticonvulsant drugs. Data were calculated and pooled across studies and expressed as standardized mean differences, odds ratios and numbers-needed-to-treat. Anticonvulsants, considered as a class, reduce migraine frequency by about 1.3 attacks per 28 days compared with placebo, and more than double the number of patients for whom migraine frequency is reduced by > or = 50% relative to placebo. Sodium valproate/divalproex sodium and topiramate were better than placebo, whereas acetazolamide, clonazepam, lamotrigine and vigabatrin were not; gabapentin, in particular, needs further evaluation. Trials designed with sufficient power to compare different drugs are also necessary.
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PMID:Anticonvulsants in migraine prophylaxis: a Cochrane review. 2041 Aug 62

Sodium valproate (VPA) is the most widely used antiepileptic drug for the treatment of epilepsy, bipolar psychiatric disorders and migraine. However, long-term VPA treatment has several adverse effects on the reproductive system. The present study was aimed to investigate the possible germ cell toxicity of VPA in mice. Animals were treated with VPA intraperitoneally for 10 and 28 days at the doses of 500 mg/kg-d and 100, 200 and 400 mg/kg-d, respectively, and were sacrificed 24h after the last dose. The germ cell toxicity of VPA was assessed using oxidative stress parameters, sperm count, sperm head morphology, sperm comet assay, 8-oxo-dG expression and histology. VPA treatment significantly decreased the sperm count, testes and epididymis weight and significantly increased the sperm head abnormality, sperm DNA damage, oxidative stress and 8-oxo-dG expression in the testes of mice. The present study illustrates that VPA induced germ cell toxicity in mice.
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PMID:Investigation on sodium valproate induced germ cell damage, oxidative stress and genotoxicity in male Swiss mice. 2200 Dec 55

About 2% of the adult population has chronic migraine with only 20% diagnosed with this disorder. Those with medication overuse may improve with withdrawal of overuse medications. The intravenous dihydroergotamine regimen usually produces short-term benefit for those with medically refractory chronic migraine. OnabotulinumtoxinA and topiramate have shown efficacy in large placebo-controlled randomized trials. Sodium valproate, gabapentin, tizanidine, amitriptyline, fluoxetine, zonisamide, and possibly memantine may be alternative or possibly combined treatment options but with lesser levels of evidence supporting their use. Preliminary evidence suggests that nerve blocks might be beneficial. Acupuncture, biofeedback, relaxation therapy, and cognitive behavioral therapy might be of benefit. Surgical treatments including bariatric and deactivation of trigger points are of growing interest but not appropriate for most sufferers. Occipital nerve stimulation is a promising treatment with ongoing studies defining its use.
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PMID:A rational approach to the management of chronic migraine. 2329 66

Migraine is a common and incapacitating neurologic disorder manifesting with episodic moderate to a severe headache and other symptoms such as photophobia, phonophobia, nausea, and vomiting. Triptans and ergot compounds have been used as treatment options for an acute migraine headache for many years. Triptans are considered the first line of treatment in patients with moderate to a severe migraine. Although the triptans are commonly used at any time during a migraine attack; they are more efficacious when used in the early stages of a migraine. Intravenous valproic acid has been shown to be well tolerated, safe, and with rapid onset of action in patients with acute moderate to severe and even refractory migraine. Sodium valproate is a Food and Drug Administration (FDA)-approved drug for prophylaxis of a migraine with and without aura. In this study, the main goal was to compare the effectiveness of sumatriptan versus valproate in an acute migraine. A randomized clinical trial including 37 patients with an acute migraine was considered to compare the effectiveness of sumatriptan versus valproate. The patients were divided into two groups. In first group, 6 mg subcutaneous of sumatriptan and in the second group 15 mg/Kg of valproate was administered. The outcomes including pain and drug adverse effects were compared across the groups. A total of 37 patients (7 male and 30 female) were evaluated in two groups. The difference between two groups regarding sex and age was not significant (P>0.05). The mean pain scores reduced from 8.3 to 4.7 and from 8.3 to 2.2 after one hour of treatment in sumatriptan and valproate groups, respectively. Response to treatment in valproate group was faster and more effective than sumatriptan group (P<0.05).The results indicated that valproate was more effective and with the faster response in patients with an acute migraine in comparison with sumatriptan without any recurrence and remarkable side effects.
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PMID:Intravenous Valproate versus Subcutaneous Sumatriptan in Acute Migraine Attack. 2661 76

Sodium valproate (VPA) is the most widely used antiepileptic drug and is increasingly also being used for several non-epileptic indications including migraines and bipolar disorder. It is known that maternal VPA exposure during pregnancy increases the risk of autism spectrum disorder (ASD) in children. Animal model studies have shown that maternal treatment with VPA in rodents conveys an increased risk for ASD-like phenotypes at the molecular, cellular, and behavioral levels. In contrast, the effect of paternal VPA exposure on behaviors in offspring is unknown. This study seeks to investigate whether paternal VPA exposure in rodents triggers behavioral and epigenetic alterations in offspring. The results show that paternal VPA exposure impairs object cognitive memory, suppresses the hyperactivity evoked by an NMDA receptor antagonist in male and female offspring, and disturbs sensorimotor gating in only females. In addition, since VPA is well known as an inhibitor of histone deacetylases, we examined the levels of acetylated histone H3 in the frontal cortex and hippocampus in the offspring of VPA-exposed sires. Interestingly, paternal VPA exposure down-regulates the levels of acetylated histone H3 in the brain in offspring even though VPA exposure increased acetylated histone H3 levels in the testes of sires. Collectively, these findings suggest that paternal VPA exposure may disturb the histone acetylation balance in the brain of offspring through changes in the germline epigenome, leading to behavioral alterations in offspring.
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PMID:Paternal valproic acid exposure in mice triggers behavioral alterations in offspring. 3165 89

Antiepileptics include various groups of drugs that have different mechanisms of actions and adverse effects. They are often also used to treat other disorders such as psychosis, chronic pain, and migraine. The most common drugs implicated in overdose include phenytoin, sodium valproate, carbamazepine, and phenobarbital. Common signs of toxicity of these drugs are central nervous system manifestations such as altered sensorium, lethargy, ataxia, and nystagmus. Some ingestions can paradoxically precipitate seizures and even status epilepticus. Sodium valproate can cause hyperammonemic encephalopathy and cerebral edema. Carbamazepine is implicated in cardiac arrhythmias and hyponatremia. Phenobarbital causes sedation, respiratory depression, and hypotension. In suspected overdose, apart from the routine laboratory tests, serum levels of the drug should be sent. Serial levels should be measured, as drug toxicity can be prolonged. Treatment of all these overdoses begins with stabilization of airway, breathing, and circulation, and endotracheal intubation being performed to protect the airway in patients with altered mental status. For decontamination, a single dose of activated charcoal should be given. Multidose of activated charcoal may be useful in phenytoin, carbamazepine, and phenobarbital overdose. Naloxone and carnitine are indicated in valproate overdose. Carbamazepine overdose can cause a widened QRS complex and arrhythmias, which can be treated with sodium bicarbonate. Forced alkaline diuresis is no longer advocated for phenobarbital poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup have formulated guidelines for extracorporeal removal of all these drugs. In most cases, hemodialysis is preferred. Other modalities include charcoal hemoperfusion (especially for carbamazepine) or continuous venovenous hemodialysis. Patients who ingest long-acting preparations should be monitored for longer periods.
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PMID:Antiepileptic Overdose. 3202 Oct 7


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