Effects of riluzole on electrically evoked neurotransmitter release

The main purpose of the present study was to investigate the effects of the neuroprotective agent riluzole on the electrically evoked release of [ 3 H]‐glutamate ([ 3 H]‐Glu) in mouse neocortical slices. The reported selectivity of riluzole for excitatory amino acids was tested in release experiments with further neurotransmitters. Also distinct species, mouse, rat and man were compared. [ 3 H]‐Glu was formed endogenously during incubation of slices with [ 3 H]‐glutamine ([ 3 H]‐Gln). Released [ 3 H]‐Glu and tissue [ 3 H]‐Glu was separated by anion exchange chromatography. Electrically evoked [ 3 H]‐Glu release was strongly diminished by tetrodotoxin (TTX) and Ca 2+ ‐withdrawal. Riluzole (100 μ M ) depressed the release of [ 3 H]‐Glu up to 77% (IC 50 =19.5 μ M ). Riluzole was also able to inhibit strongly the electrically evoked release of [ 3 H]‐acetylcholine ([ 3 H]‐ACh) (at 100 μ M by 92%, IC 50 =3.3 μ M , and [ 3 H]‐dopamine ([ 3 H]‐DA) (at 32 μ M by 72%, IC 50 =6.8 μ M ). However, the release of [ 3 H]‐serotonin ([ 3 H]‐5‐HT) was less diminished (at 100 μ M by 53%, IC 50 =39.8 μ M ). Riluzole up to 100 μ M did not affect [ 3 H]‐noradrenaline ([ 3 H]‐NA) release. Between species, i.e. in mouse, rat and human neocortex, no significant differences between the effects of riluzole could be observed. The NMDA‐receptor blocker MK‐801 (1 μ M ) and the AMPA/Kainate‐receptor blocker NBQX (1 μ M ) did neither affect the electrically evoked [ 3 H]‐ACh release nor its inhibition by riluzole, indicating that effects of riluzole on transmitter release were neither due to modulation of ionotropic Glu receptors, nor due to indirect inhibition of Glu release through these receptors. Taken together, riluzole inhibits the release of distinct neurotransmitters differently, but is not selective for the excitatory amino acid Glu.British Journal of Pharmacology (2000) 130 , 1227–1234; doi: 10.1038/sj.bjp.0703424