A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer's Disease

Molecules. 2019 Nov 25;24(23):4298. doi: 10.3390/molecules24234298.


The orphan drug dantrolene (DAN) is the only therapeutic treatment for malignant hyperthermia (MH), a pharmacogenetic pathology affecting 0.2 over 10,000 people in the EU. It acts by inhibiting ryanodine receptors, which are responsible for calcium recruitment in striatal muscles and brain. Because of its involvement in calcium homeostasis, DAN has been successfully investigated for its potential as neuroprotecting small molecule in several animal models of Alzheimer's disease (AD). Nevertheless, its effects at a molecular level, namely on putative targets involved in neurodegeneration, are still scarcely known. Herein, we present a prospective study on repurposing of DAN involving, besides the well-known calcium antagonism, inhibition of monoamine oxidase B and acetylcholinesterase, cytoprotection from oxidative insult, and activation of carnitine/acylcarnitine carrier, as concurring biological activities responsible for neuroprotection.

Keywords: Alzheimer’s disease; carnitine/acylcarnitine carrier; dantrolene; drug repurposing; multitarget activity; neuroprotection.

MeSH terms

  • Acetylcholinesterase / drug effects
  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Calcium / metabolism*
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / pharmacology
  • Carnitine / analogs & derivatives
  • Carnitine / metabolism
  • Cell Line
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Dantrolene / chemistry
  • Dantrolene / pharmacology*
  • Drug Repositioning
  • Humans
  • Malignant Hyperthermia / drug therapy
  • Monoamine Oxidase / chemistry
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*


  • Calcium Channel Blockers
  • Cholinesterase Inhibitors
  • Monoamine Oxidase Inhibitors
  • Neuroprotective Agents
  • acylcarnitine
  • Monoamine Oxidase
  • Acetylcholinesterase
  • Dantrolene
  • Carnitine
  • Calcium

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