How did we discover Phenytoin Cream?

We read the books of the Wallstreet tycoon Jack Dreyfuss, ‘the story of a remarkable medicine‘, where he presented Phenytoin as a very special drug. He subsequently created a foundation, the Dreyfus Medical Foundation.

That foundation created a book on ‘the broad range of clinical use of Phenytoin’. In that book many chapters on the remarkable properties of it, amongst others as a painkiller for

• postherpetic neuralgia
• dysesthesia
• trigeminal neuralgia
• CRPS, and may other
• pain syndromes

The foundation also added a chapter on Phenytoin as a preventive. This provoked us to look into the protective properties of this drug.

We found out that it has been explored as a cytoprotective and neuroprotective drug already many decades ago.

In the article ‘How to Define Neuroprotection: The Case of Phenytoin’, we discussed many of the neuroprotective experiments with this special molecule.

Neuroprotection

We subsequently started a collaboration with Italian eye specialists, as there were clear indicators for retinaprotection. We understood that retinaprotection and protection of the small unmyelated fibers in the skin will have many similarities.

And that the retina can serve as a model to test the neuroprotective properties of this for small fibers.

This paper was published in the Britisch Journal of Clinical Pharmacology and was one of our keystone papers supporting the idea of a analgesic+ cream.

In pain medicine we do not want analgesia alone, we want protection of the degenerating nerve fibers. Phenytoin might very well be such disease-modifying analgesic drug.

 

 

May 2019, prof. dr. Jan M. Keppel Hesselink, MD, PhD, painspecialist

Sources

4 articles supporting Phenytoin’s neuroprotective spectrum of actions

• Keppel Hesselink JM, Kopsky DJ. Phenytoin: neuroprotection or neurotoxicity? Neurol Sci. 2017 Jun;38(6):1137-1141.
• Keppel Hesselink JM. How to Define Neuroprotection: The Case of Phenytoin. Open Access J Neurol Neurosurg. 2018; 7(4): 555719.
• Chiosi F, Keppel Hesselink JM, Rinaldi M, Di Staso S, Bartollino S, Costagliola C. Phenytoin: its potential as neuroprotective and retinoprotective drug. Br J Clin Pharmacol. 2017 Oct 12.
• Keppel Hesselink JM, Kopsky DJ. Phenytoin: neuroprotection or neurotoxicity? Neurol Sci. 2017 Jun;38(6):1137-1141.