Phenytoin Reduces Cognitive Deficits Post-Covid?
A glimpse at one mechanism behind the impairment.
Here’s an interesting study that looked at what prescriptions a group of people with epilepsy were taking at the time of infection - it found that those who were on phenytoin were 22% less likely to have cognitive deficits (like ‘brain fog’) compared to people taking 2 other drugs.
“Exposure to phenytoin associates with a lower risk of post-COVID cognitive deficits: a cohort study.” Brain Communications, 22 Aug 2022, PMID 35999838.
We don’t know at this time if phenytoin would have any effects if taken after a long covid condition sets in, the study was not designed to test that possibility.
Phenytoin is also known as Dilantin. The molecule is known to block “receptor-interacting protein kinase.” Kinases are a category of enzymes that transfer phosphate groups from things like ATP to proteins (like receptors and enzymes) and that phosphate group changes the biological activity of the protein. In the case of epilepsy, phenytoin is used to block this phosphate transfer, and that can reduce the frequency of epileptic activity. In general, adding a phosphate to a receptor activates it, it makes it function at a higher level. But proteins can also get too many phosphate groups added to them, and that hyper-phosphorylation can reduce their activity.
There are many different families of receptors that are phosphorylated by kinases. One group of receptors that may be involved in long covid are those for Vascular Epidermal Growth Factor (VEGF). People with long covid typically have a reduced number of very small capillaries (which reduces oxygen and nutrient flow) - I wrote about VEGF here: Capillary Density Drops in Long Covid. Speculation here: it is possible that being infected with the SARS2 virus leads to over-phosphorylation of these receptors, and that reduces the activity of the VEGF system. Maybe. Hyperphosphorylation may be one mechanism that contributes to Alzheimer’s disease and other neurological disorders.
In the study, phenytoin had a relatively modest effect - it reduces the number of long haulers with cognitive impairment by about 22%. And it can have serious side effects, so it is unlikely that doctors will be quick to prescribe it to people who only report brain fog. Wikipedia has a decent article on Phenytoin. It’s an interesting medicine, but not one I would want to take unless there was no other choice. But this study may point to the molecular basis of some of the cognitive impairment that is so prevalent with post-covid conditions. There may be another receptor kinase inhibitor that is more effective, with lower toxicity.