It is commonly known that some medicines are counter-indicated by sodium channelopathies. One of that medicines is Phenytoin (PH). But I know some patients, harboring truncating SCN1A mutations, for whom PH helped. Are there any studies about different types of medical treatment for nonsense- and missense-mutations of SCN1A gene?
Or can anyone suggest the biochemical causes of such medicine's behaviour?
Hi Roman,
There is a study suggesting that phenytoin may prevent NMDA receptor hypofunction neurotoxicity by inhibiting voltage-gated sodium channels. This is supported by the observation that TTX produced similar effects. Here is the study:
Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity http://www.ncbi.nlm.nih.gov/pubmed/12192617
On the other hand, phenytoin influence the surface trafficking of VGSCs, so you have here a confounding effect (http://www.ncbi.nlm.nih.gov/pubmed/17928445)
Hope this helps. Norbert
Dear Norbert.
Thanks for advice. I will deeply examine the sources, you've mentioned.
Hi Roman
This depends on the functional effect of the sodium channelopathy.
Pathogenic variants
- in SCN1A generally have a LOF (loss of function) effect
- in SCN2A might have either a LOF or GOF (gain of function) effect
- in SCN8A developmental and epileptic encephalopathy (DEE) have most often a GOF effect
PHT is a powerful sodium channel blocker, therefore it is generally contraindicated in SCN1A-Dravet sd, but is very useful for SCN8A-DEE.
A few patients with SCN1A GOF MISSENSE variant have been described. Those patients might benefit from PHT treatment.
Best
Elena
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