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A pilot trial of dextromethorphan in amyotrophic lateral sclerosis
H Askmark1, S M Aquilonius, P G Gillberg
1University Hospital, Uppsala, Sweden.
Abstract:
Assuming the presence of glutamate-induced neurotoxicity in amyotrophic lateral sclerosis 14 patients were treated with dextromethorphan, an N-methyl-D-aspartate receptor antagonist. The patients were treated with 150 mg dextromethorphan or placebo daily for 12 weeks in a double-blind crossover trial, with a wash out period of 4 weeks between the two treatment periods. Thereafter the surviving patients were treated with 300 mg dextromethorphan daily for up to 6 months in an open trial. No positive effects on clinical or neurophysiological parameters (relative number of axons, and compound muscle action potentials in the abductor digiti minimi muscle) were observed either in the double-blind trial or in the open trial.
Insights
Dextromethorphan, an N-methyl-D-aspartate receptor antagonist, was tested in amyotrophic lateral sclerosis patients. The drug showed no positive effects on clinical or neurophysiological measures in this study.
Area of Science:
- Neuroscience
- Neurology
- Pharmacology
Background:
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
- Glutamate excitotoxicity is a proposed mechanism in ALS pathogenesis.
- N-methyl-D-aspartate (NMDA) receptors are implicated in excitotoxicity.
Purpose of the Study:
- To investigate the efficacy of dextromethorphan, an NMDA receptor antagonist, in treating ALS patients.
- To assess the impact of dextromethorphan on clinical and neurophysiological parameters in ALS.
Main Methods:
- A double-blind, placebo-controlled crossover trial involving 14 ALS patients treated with 150 mg dextromethorphan or placebo daily for 12 weeks.
- A subsequent open-label trial where surviving patients received 300 mg dextromethorphan daily for up to 6 months.
- Neurophysiological assessments included the relative number of axons and compound muscle action potentials in the abductor digiti minimi muscle.
Main Results:
- Dextromethorphan did not demonstrate any positive effects on clinical outcomes.
- No improvements were observed in neurophysiological parameters, such as the relative number of axons or compound muscle action potentials.
- Both the double-blind and open-label treatment phases yielded negative results.
Conclusions:
- Dextromethorphan, at the tested dosages and duration, is not effective in treating amyotrophic lateral sclerosis.
- The study does not support the hypothesis that NMDA receptor antagonism with dextromethorphan benefits ALS patients.
- Further research into alternative therapeutic strategies for ALS is warranted.