Riluzole enhances glutamate uptake in rat astrocyte cultures

Cell Mol Neurobiol. 2004 Feb;24(1):123-8. doi: 10.1023/b:cemn.0000012717.37839.07.


1. Riluzole is used for the treatment of amyotrophic lateral sclerosis and reported to have neuroprotective effects in animal models of Parkinson's disease, Huntington's disease, and brain ischemia. The neuroprotective action of riluzole has been attributed to its ability to inhibit glutamate release (A. Doble, Neurology 47(4):233S-241S, 1996). 2. The effect of riluzole on L-[2,3-3H] glutamate uptake was investigated in rat cortical astrocyte cultures. 3. Riluzole showed a biphasic concentration-dependent effect on basal glutamate uptake. At low concentrations (1 and 10 microM) riluzole significantly increased glutamate uptake, whereas from 100 microM promoted a slight reduction. 4. Considering the large range of glutamate levels in the synaptic cleft, we studied the 1 microM riluzole effect on uptake of glutamate at different concentrations (1-1000 microM). Riluzole was more effective at low glutamate concentrations (10 microM), enhancing the basal glutamate uptake up to 42%. 5. The action of riluzole on astrocytic glutamate uptake could be an additional mechanism to its neuroprotective role, perhaps suggesting a modulatory action on glutamatergic system involving glutamate clearance from synaptic cleft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Glutamic Acid / metabolism*
  • Glutamic Acid / pharmacokinetics
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Riluzole / pharmacology*
  • Synapses / drug effects*
  • Synapses / metabolism
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology


  • Neuroprotective Agents
  • Glutamic Acid
  • Riluzole