2004 issue 1

Back

Volume 13, issue 1

Review article

Neuroprotective properties of memantine in pre-clinical studies

EWA TARACHA1, MAŁGORZATA LEHNER2, Adam Płaźnik1,2
1. Katedra i Zakład Farmakologii Doświadczalnej i Klinicznej w Warszawie
2. Zakład Neurochemii Instytutu Psychiatrii i Neurologii w Warszawie
Postępy Psychiatrii i Neurologii, 2004, 13 (1), 37-49
Keywords: dementia, neurodegeneration, NMDA receptor, memantine

Abstract

Aim. Loss of neurons, most/y cholinergic, is a common feature of Alzheimer's and other neurodegenerative diseases. Excitotoxic reactions related to an excess glutamate release in the CNS probably contribute to cell death. There is a need for agents that prevent or inhibit the process of dementia, so drugs that slow the disease progression are urgently needed.

Review. NMDA receptors mediate fast excitatory synaptic transmission in the CNS, and are involved in learning and memory processes. These receptors comprise a ligand-gated ion channel that is permeable to Ca²+. In pathological conditions, an altered calcium homeostasis in neurons may result in cell death, and calcium-dependent neurotoxicity is thought to derive from an excessive activation of NMDA receptors. Thus, antagonists at NMDA receptors may prevent cell death and retard the progression of symptoms in patients with dementia. Many pre-clinical and clinical observations indicate the therapeutic utility of memantine. Memantine has been proved to be a non-competitive NMDA receptor antagonist, with sufficient affinity to block the CNS NMDA receptors at therapeutic doses.

Conclusions. In animal models memantine can protect against the excitotoxic destruction of neurons, and at clinically relevant concentrations memantine promotes synaptic plasticity and preserves or enhances memory functions. Consequently, the drug has received a considerable attention in recent years in the treatment of dementia.

Address for correspondence:
Adres: Dr Ewa Taracha,
Zakład Neurochemii Instytutu Psychiatrii i Neurologii,
ul. Sobieskiego 9,
02-957 Warszawa,
tel. (0-22) 3213319, fax: 3213471, e-mail: taracha@ipin.edu.pl