Friday, March 6, 2009



Valproic acid (VPA) is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and less commonly major depression. It is also used to treat migraine headaches and schizophrenia.


Valproate is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain, making it an alternative to lithium salts in treatment of bipolar disorder.In addition to blocking transamination of GABA, Valproate is believed to reverse the transamination process to form more GABA. However, several other mechanisms of action in neuropsychiatric disorders have been proposed for valproic acid in recent years..
Valproic acid also blocks the
voltage-gated sodium channels and T-type Calcium channels.These mechanisms make Valproic Acid a Broad Spectrum Anticonvulsant drug.
Valproic acid is an
inhibitor of the enzyme histone deacetylase 1 (HDAC1) hence it is a histone deacetylase inhibitor.

Why in Neuro:-

As an anticonvulsant, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, juvenile myoclonic epilepsy and the seizures associated with Lennox-Gastaut syndrome. It is also used in treatment of myoclonus. In some countries, parenteral (administered intravenously) preparations of valproate are used also as second-line treatment of status epilepticus, as an alternative to phenytoin. Valproate is one of the most common drugs used to treat post-traumatic epilepsy.


Valproate is relatively contraindicated in pregnancy due to its teratogenicity; women who become pregnant while taking valproate should be counselled as to its risks, take high dose folic acid and be offered antenatal screening (alpha-fetoprotein and second trimester ultrasound scans).It is a known folate antagonist, which can cause neural tube defects. Thus, folic acid supplements may alleviate the teratogenic problems. A recent study showed that children of mothers taking valproate during pregnancy are at risk for significantly lower IQs. Exposure of the human embryo to valproic acid is also associated with risk of autism, and it is possible to duplicate features characteristic of autism by exposing rat embryos to valproic acid at the time of neural tube closure. One study found that valproate exposure on embryonic day 11.5 led to significant local recurrent connectivity in the juvenile rat neocortex, consistent with the underconnectivity theory of autism.
Valproate is contraindicated in overweight patients because it might cause weight gain.[
citation needed]

Common Side Effects:-

Common side effects are dyspepsia and/or weight gain. Less common are fatigue, peripheral edema, acne, dizziness, drowsiness, hair loss, headaches, nausea, sedation and tremors. Valproic acid also causes hyperammonemia, which can lead to brain damage.Valproate levels within the normal range are capable of causing hyperammonemia and ensuing encephalopathy. There have been reports of brain encephalopathy developing without hyperammonemia or elevated valproate levels

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