Riluzole is an antiexcitotoxic agent 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. We investigated the effects of riluzole on synthesis of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in cultured mouse astrocytes. The protein and mRNA levels were measured by enzyme-linked immunosorbent assay and semiquantitative reverse transcription-polymerase chain reaction, respectively. Treatment with riluzole at 100 microg/ml (426 microM) for 24 h increased the contents of NGF, BDNF, and GDNF in the culture medium 109-fold, 2.0-fold and 3.1-fold over the control, respectively. The drug-induced relative mRNA levels of NGF, BDNF, and GDNF were 7.3-fold at 2 h, 2.1-fold at 4 h, and 1.9-fold at 2 h, respectively. These results indicate that riluzole stimulates synthesis of NGF, BDNF and GDNF in cultured astrocytes. Riluzole might exert neuroprotective effects, at least in part, via stimulation of neurotrophic factors.