RILUZOLE - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES AND THERAPEUTIC POTENTIAL IN AMYOTROPHIC-LATERAL-SCLEROSIS

Riluzole, a benzothiazole, affects neurons by 3 mechanisms: by inhibit ing excitatory amino acid release, inhibiting events following stimula tion of excitatory amino acid receptors and stabilising the inactivate d state of voltage-dependent sodium channels. It has demonstrated neur oprotective activity in vivo and in vitro. Results from 2 randomised d ouble-blind placebo-controlled trials in patients with amyotrophic lat eral sclerosis (ALS; motor neuron disease) have demonstrated the riluz ole can extend survival and/or time to tracheostomy. After 18 months, the relative risk of death or tracheostomy with riluzole 100 mg/day wa s reduced by 21%. Although riluzole slowed the rate of deterioration i n muscle strength in the first trial, this was not confirmed in the se cond, larger trial. Riluzole had no effect on any other functional or secondary variable. Gastrointestinal effects, anorexia, asthenia, circ umoral paraesthesia and dizziness were reported more frequently with r iluzole than placebo. Elevated alanine aminotransferase levels were ob served in 10.6 versus 3.8% of patients treated with riluzole 100 mg/da y versus placebo, leading to treatment withdrawal in 3.8 versus 2.1% o f patients. In conclusion, riluzole is the first drug that has been sh own to have an effect on survival in patients with ALS. Although the e ffect of riluzole was modest, it has allowed some insight into the pat hogenesis of ALS for which future gains may be made.