New clues about how valproic acid (sodium valproate) works in the brain have been suggested in work by researchers from Stanford University in California, USA. Valproic acid is unusual among anti-epilepsy drugs (AEDs) because it is effective against several different types of seizures, including absence seizures, partial seizures and generalised tonic-clonic seizures. It is consequently a widely-prescribed drug. Exactly how it works - which receptors in which cells it interacts with in the brain - remains a mystery however. Several possible mechanisms have been suggested, and this research adds another.

The anti-epileptic effects of valproic acid were discovered by chance in 1963. Researchers in France were testing a batch of different candidate compounds for anti-epileptic activity, and found many of them showed identical properties. The reason: all the candidate compounds were dissolved in valproic acid, which is still used as a solvent today. It was the solvent, and not what was dissolved in it, that worked against the seizures.

Dr Brill and colleagues found that steady administration of valproic acid over several days boosted the levels of a compound called neuropeptide Y in the brain by about 50%. Surprisingly, these levels were increased in two parts of the brain only: the thalamus and the temporal lobe. These two sections of the brain are those most associated with the types of seizures valproic acid works best against.

The thalamus is very important for transferring information from one area of the brain to another, allowing connections to be made. In particular it transfers input from the senses (except smell) and transmits it to the cerebral cortex (the grey matter, or higher thinking area). The temporal lobe is highly involved with processing auditory signals, which in humans includes understanding speech.

Neuropeptides are small proteins that help to transmit signals between brain cells, in parallel to the work of neurotransmitters. Neuropeptide Y has anti-convulsive properties, as fewer epileptic-type patterns were seen in the electrical activity of the valproic acid-treated brains when tested. The concentrations of other neuropeptides were not changed by the administration of valproate. The research was published in June in the Journal of Neuroscience.

Exactly how valproic acid triggers production of neuropeptide Y is still unknown. However, Dr Brill suggested that it may be possible to design drugs that increase the production of neuropeptide Y and prolong its presence and action in the brain. This could have the same therapeutic effect as valproic acid but not its side effects.

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