Memantine in the Treatment of Neurological Diseases: Lessons from Multiple Sclerosis

Review Article


Gonzalo Arrondo ¹, Manuel Alegre ¹ and Pablo Villoslada ²
Affiliations: ¹Department of Neurosciences, CIMA— University of Navarra, Navarra, Spain and ²Department of Neurosciences, Institute for Biomedical Research August Pi Sunyer—Hospital Clinic of Barcelona, Barcelona, Spain

ABSTRACT

Memantine, an uncompetitive, low‐affinity N‐methyl‐D‐aspartate (NMDA) receptor antagonist, is an approved compound for use in moderate to severe Alzheimer’s disease. Its pharmacological features allow it to block excessive neuronal activation produced by glutamate, while permitting normal activation of the NMDA receptor channel. A review of the trials that have evaluated the use of the compound in vascular dementia, Alzheimer’s disease, or both shows that it is well tolerated and has mild but statistically significant positive effects on cognition and other domains of patients with advanced Alzheimer’s disease. Recently, a double‐blind, placebo‐controlled trial in patients with multiple sclerosis reported neurological worsening in several patients similar to the typical pseudoexacerbations of this disease. Also, the use of memantine in patients with Lewy body disease produces adverse effects. Although the mechanisms of such side‐effects are unknown, we suggest that they could be due to the impairment of synaptic transmission in the demyelinated pathways.

Keywords: Memantine, multiple sclerosis, Alzheimer’s disease, Lewy bodies dementia, clinical trial, block conduction, pseudoexacerbations, side‐effects
Correspondence: Pablo Villoslada, Department of Neurology, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. e‐mail: pvilloslada@clinic.ub.es