Donepezil ameliorates oxaliplatin-induced peripheral neuropathy via a neuroprotective effect

J Pharmacol Sci. 2019 Jul;140(3):291-294. doi: 10.1016/j.jphs.2019.05.009. Epub 2019 Jul 19.

Abstract

Oxaliplatin induces severe peripheral neuropathy. The effect of donepezil, a drug used for treatment of Alzheimer's disease, on oxaliplatin-induced peripheral neuropathy was investigated using both in vivo and in vitro models. Donepezil effectively attenuated oxaliplatin- and cisplatin-induced inhibition of neurite outgrowth in cultured PC12 cells. In a rat model, repeated oral administration of donepezil (5 times/week for 4 weeks) ameliorated oxaliplatin-induced mechanical allodynia (von Frey test) and sciatic nerve axonal degeneration. Moreover, donepezil did not inhibit the anti-tumor activity of oxaliplatin in any cultured cancer cell line. Therefore, donepezil may be useful for managing oxaliplatin-induced peripheral neuropathy.

Keywords: Donepezil; Oxaliplatin; Peripheral neuropathy.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Donepezil / pharmacology*
  • Male
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Oxaliplatin / pharmacology*
  • PC12 Cells
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / drug effects

Substances

  • Antineoplastic Agents
  • Neuroprotective Agents
  • Oxaliplatin
  • Donepezil