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KMID : 1130620070030040181
Journal of Clinical Neurology
2007 Volume.3 No. 4 p.181 ~ p.186
Oral Administration of Memantine Prolongs Survival in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis
Joo In-Soo

Hwang Dong-Hoon
Seok Jung-Im
Shin Sang-Kun
Kim Seung-Up
Abstract
Background and Purpose: N-methyl-D-aspartate (NMDA)-mediated neurotoxicity and oxidative stress have been implicated in the etiology of amyotrophic lateral sclerosis (ALS). Memantine is a low-affinity, noncompetitive NMDA receptor antagonist that may protect against motor neuron degeneration.

Methods: Thirty transgenic mice expressing the G93A SOD1 mutation were randomly divided into control, low- dose memantine (30 mg/kg/day), and high-dose memantine (90 mg/kg/day) groups, with memantine supplied daily with drinking water beginning at 75 days of age. Body weight, survival, and behavioral performances including a rotarod test, paw grip endurance, and hindlimb extension reflex were assessed in the control and memantine-diet groups.

Results: Clinical symptoms were evident in the G93A transgenic mice by 11 weeks of age. Memantine was tolerated well. Compared to control, mice treated with memantine performed better in the rotarod test and hindlimb extension reflex. Moreover, low-dose memantine treatment significantly prolonged the survival of the transgenic mice relative to control mice (141 vs 134 days, p<0.05).

Conclusion: These findings suggest that memantine, even when administered at the time of symptom onset, has beneficial effects on patients with ALS
KEYWORD
Amyotrophic lateral sclerosis, Memantine, N-methyl-D-aspartate receptor antagonist
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