Clinical trials of riluzole in patients with ALS
Abstract
Two double-blinded, placebo-controlled clinical trials of riluzole have now been carried out in more than 1,100 patients with ALS. The results of both studies show a modest benefit in prolonging survival that is statistically significant. These results led to the availability of this drug by the Food and Drug Administration for use in the United States beginning in early 1996. This is the first drug that has been available for ALS. It begins a new era in both basic and clinical research in an attempt to find a cure for this disease.
NEUROLOGY 1996;47(Suppl 2): S86-S92
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REFERENCES
1.
Rothman SM, Thurston JH, Hauhart RE. Delayed neurotoxicity of excitatory amino acids in vitro. Neuroscience 1987;22:471-480.
2.
Choi DW. Glutamate neurotoxicity and disease of the nervous system. Neuron 1988;1:623-634.
3.
Plaitakis A, Caroscio JT. Abnormal glutamate metabolism in ALS [abstract]. Ann Neurol 1985;18:165.
4.
Plaitakis A, Caroscio JT. Abnormal glutamate metabolism in amyotrophic lateral sclerosis. Ann Neurol 1987;22:575-579.
5.
Perry TL, Hansen S, Jones K. Brain glutamate deficiency in amyotrophic lateral sclerosis. Neurology 1987;37:1845-1848.
6.
Plaitakis A, Constantakakis E, Smith J. The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosis. Ann Neurol 1988;24:446-449.
7.
Rothstein JD, Martin LJ, Kuncl RW. Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 1992;326:1464-1468.
8.
Rothstein J, Van Kammen M, Levey AI, Martin LJ, Kuncl RW. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 1995;38:73-84.
9.
Rothstein JD, Jin L, Dykes-Hoberg M, Kuncl RW. Chronic glutamate uptake inhibition produces a model of slow neurotoxicity. Proc Natl Acad Sci USA 1993;90:6591-6595.
10.
Estevez AG, Stutzmann JM, Barbeito L. Protective effect of riluzole on excitatory amino acid-mediated neurotoxicity on motoneuron-enriched cultures. Eur J Pharmacol 1995;280:47-53.
11.
Rothstein JD, Kuncl RW. Neuroprotective strategies in a model of chronic glutamate-mediated motor neuron toxicity. J Neurochem 1995;65:643-651.
12.
Hubert JP, Delumeau JC, Glowinski J, et al. Antagonism by riluzole of entry of calcium evoked by NMDA and veratridine in rat cultured granule cells: evidence for a dual mechanism of action. Br J Pharmacol 1994;113:261-267.
13.
Herbert T, Drapeau P, Pradier L, et al. Block of the rat brain IIA sodium channel alpha subunit by the neuroprotective drug riluzole. Mol Pharmacol 1994;45:1055-1060.
14.
Bensimon G, Lacomblez L, Meininger V, ALS/Riluzole Study Group. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med 1994;330:585-591.
15.
Lacomblez L, Bensimon G, Leigh PN, ALS/Riluzole Study Group II. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Lancet 1996;347:1425-31.
16.
Tarone RE. Tests for trend in life Table analysis. Biometrika 1975;62:679-682.
17.
Horowitz S, Patwardhan R, Marcus E. Hepatotoxic reactions associated with carbamazepine therapy. Epilepsia 1988;29:149-154.
18.
Amato MP, Pracucci G, Ponziani G, Siracusa G, Fratiglioni L, Amaducci L. Long-term safety of azathioprine therapy in multiple sclerosis. Neurology 1993;43:831-833.
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Neurology®
Volume 47 • Number 4_suppl_2 • October 1996
Pages: 86S-92S
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Copyright 1996 by Advanstar Communications Inc.
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Published online: October 1, 1996
Published in print: October 1996
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