ABSTRACT
Recent studies provide new insights into the molecular and cellular processes leading to selective motor neuron death in ALS. Proposed mechanisms of pathogenesis include glutamate toxicity, oxidative stress, apoptosis, cytotoxicity, protein aggregation and neuroinflammation. The excitotoxicity theory was first proposed in the early 1970s to describe neurodegeneration resulting from excessive exposure to excitatory amino acids. Riluzole was originally developed as an anticonvulsant. The drug inhibits the pre-synaptic release of glutamate and reduces neuronal damage in several experimental models. Riluzole had a significant effect on rates of survival and muscle strength deterioration. The safety concerns for riluzole are relatively few, with side-effects mainly confined to fatigue, nausea or vomiting, and very occasionally elevated liver enzymes, renal function impairment, vertigo or somnolence. Gabapentin Studies suggest that the anticonvulsant gabapentin may reduce glutamate activity, but its exact mechanism of action upon the glutamatergic system has not been fully elucidated.
