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August 23, 2026MedicinesOpen Access

Beyond the Central Nervous System: Uncovering Memantine’s Modulatory Role in the Peripheral Nervous System

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Authors

KPKyriaki PapadopoulouSTSophia TsokkouIKIoannis Konstantinidis

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Overview

Narrative review demonstrates neuroprotective and analgesic actions of memantine in peripheral neuropathies, indicating broad therapeutic potential beyond Alzheimer's disease.

Key Points

  • To synthesize preclinical and clinical evidence on the neuroprotective and modulatory mechanisms of memantine in the peripheral nervous system and evaluate drug repurposing opportunities.
  • Narrative synthesis of preclinical mechanistic studies and clinical trials evaluating memantine actions on peripheral sensory and autonomic neurons, Schwann cells, and retinal ganglion cells.
  • Evaluated pathological pathways including excitotoxic calcium influx, oxidative injury, mitochondrial dysfunction, apoptotic signaling, and neuroinflammation.
  • Memantine consistently attenuates peripheral excitotoxic calcium influx, suppresses NOX-2-mediated reactive oxygen species, stabilizes mitochondrial membrane potential, and reduces neuroinflammatory cytokine activity.
  • Clinical evidence highlights a five-fold reduction in post-mastectomy neuropathic pain with pre-emptive administration, alongside reduced phantom limb pain intensity at six months and enhanced diabetic neuropathy management combined with gabapentin.

Cite This Study

Papadopoulou et al. (2026) studied this question.

synapsesocial.com/papers/6a8aae507677a34114447455https://doi.org/10.3390/medicines13030025
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