I have seen it said that the precise mechanism of action of migraine medicine Topiramate is not known. But I certainly see a resemblance between that molecule and PLP (Pyridoxal phosphate, the activated form of vitamin B6).

The molecular structure of topiramate

A significant similarity is that both have an "offshoot chain" (Topiramate's sulfamate taking the place of PLP's phosphate) where PLP's phosphate is what binds it to enzymes in the first place, and both have a more electronegative element in the middle of what would otherwise be a six-carbon ring, apparently important in the typical PLP enzyme reaction.

The molecular structure of pyridoxal phosphate

I have been wondering if Topiramate supplants PLP in the enzyme glutamate decarboxylase, changing the reaction into a deamination. This would deplete glutamate, causing the pill's migraine relief, and the deamination could even cause Topiramate hyperammonemia.

If it does the same or similar to serine hydroxymethyltransferase, which is also PLP dependent, it could cause glycine deficiency, thus collagen deficiency - and this would even explain Topiramate hair loss.

When you look at it this way, it's frankly hard to imagine the mechanism of action is anything different. Have I stumbled upon it? Or has this been suggested already?


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