Phenytoin: neuroprotection or neurotoxicity?

Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Jan M Keppel Hesselink, David J Kopsky

Abstract

Phenytoin is an 80-year young molecule and new indications are still emerging. The neuroprotective potential of phenytoin has been evaluated for decades. Recently, a positive phase II trial supported its further development in the treatment of optic neuritis in multiple sclerosis. In 1942, however, peripheral neuritis was first reported to be an adverse event of phenytoin, and since then a small but steady stream of publications discussed peripheral polyneuropathy as being a possible adverse event of phenytoin. We have reviewed the literature and concluded there is some supportive evidence for a reversible polyneuropathy after the oral use of phenytoin, though with no evidence for clear neurotoxicity on the level of peripheral nerves. This is probably due to the fact that the pharmacological effects of phenytoin, based on the stabilizing effect of the voltage-gated sodium channels, make impairment of nerve conduction in asymptomatic and symptomatic reversible polyneuropathies plausible. Clear toxically-induced phenytoin-related polyneuropathies, however, are extremely rare and are always related to high dose or high plasma levels of phenytoin, mostly developing during many years of therapy. We could only find one case of a prob...Continue Reading

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Citations

Jan 13, 2018·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Ilaria Di Donato, Antonio Federico
Mar 3, 2020·Journal of Pain & Palliative Care Pharmacotherapy·Alan L RussellJan M Keppel Hesselink
May 31, 2018·Pharmaceuticals·David J Kopsky, Jan M Keppel Hesselink
Jul 25, 2021·International Journal of Molecular Sciences·Federica CherchiElisabetta Coppi

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