Novel epilepsy drugs identified

New treatments for epilepsy may become possible thanks to research carried out on zebrafish.

Researchers led by Dr Vincent Cunliffe of Sheffield University, UK, used zebrafish which had been exposed to a convulsant agent as embryos, and went on to have epileptic seizures.

This "provides opportunities to identify novel anticonvulsants for the treatment of people with epilepsy," explain the team in the journal Disease Models and Mechanisms.

They say that exposure to the convulsant agent pentylenetetrazole "rapidly induces the expression of synaptic-activity-regulated genes in the central nervous system, and elicited vigorous episodes of calcium flux in muscle cells as well as intense locomotor activity".

They went on to identify 46 bioactive molecules from a group of about 2,000 that suppressed these changes made to the zebrafish. Many of the compounds are known to have anticonvulsant properties.

Further analysis of a sub-group of these compounds showed that they held back locomotor activity and pentylenetetrazole-induced fos transcription, "confirming their anticonvulsant characteristics".

The researchers believe this approach is a reliable way of seeing the neural response to convulsant treatments, and could be very useful in future. In particular, this way of seeing which compounds suppress pentylenetetrazole-induced fos expression "provides a sensitive means of identifying compounds with anticonvulsant activities".

Dr Cunliffe said: "Some of the identified compounds already have a variety of different medical uses in treating conditions such as fungal infections, as well as psychiatric and inflammatory disorders."

If human trials are successful, some of these existing drugs could be used in the treatment of epilepsy.

Baxendale, S. et al. Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures. Disease Models and Mechanisms November 2012 doi: 10.1242/dmm.010090

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