of the central nervous system in a few con-ditions\p=m-\thecerebral cortex in Alzheimer's disease and the senile psychoses, and the substantia nigra and brain stem in parkinsonism.Recent observations of neurofibrillary changes in 2 fatal neurologic diseases occurring on the island of Guam, the parkinsonism-dementia complex (Hirano, Kurland, Krooth, and Lessell 1; Hirano, Malamud and Kurland 2) and the amyotrophic lateral sclerosis syndrome (Malamud, Hirano and Kurland3), revealed their quite remarkable numbers and symmetric distribution in certain parts of the central nervous system. A combination of these 2 syndrome complexes

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This chapter was originally intended to cover both amyotrophic lateral sclerosis (ALS) and multiple sclerosis, but we will concentrate on ALS. There are nonetheless several reports from the literature that ionotropic glutamate receptor antagonists have beneficial effects in animal models of multiple sclerosis (1,7,14,58,71,109) and this could develop into a very promising therapeutic area in the future. The interested reader is referred to the following review (59). However, the evidence for involvement of disturbances in the glutamatergic system in ALS is already convincing and has led to the use of the glutamate release inhibitor riluzole in the treatment of this disease. As such, we felt that a book on the therapeutic potential of ionotropic glutamate receptor antagonists and modulators would be incomplete without a chapter on this disease. RATIONALEALS, commonly called Lou Gehrig's disease, is a devastating neurological disorder characterized by selective upper and lower somatic, but not autonomic, motor neurone degeneration leading to paralysis and eventually death. The diagnosis of ALS requires the presence of both upper and lower motor neurone degeneration and progressive motor dysfunction. ALS occurs in 1 to 2.5 cases per 100,000 population, affects more men than women, and is most commonly diagnosed in middle age. Other functions such as intellectual abilities and sensory perception are preserved. At advanced stages patients become completely disabled, often requiring ventilatory support and feeding by gas-

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