Memantine

Memantine is the first in a novel class of Alzheimer's disease medications acting on the glutamatergic system. Memantine was developed by Merz and licensed to Forest for the U.S. and Lundbeck for selected European and international markets. Memantine is marketed under the brands Axura and Akatinol by Merz, Namenda by Forest and Ebixa by Lundbeck.

Pharmacology

Glutamatergic (NMDA receptor)

A dysfunction of glutamatergic neurotransmission, manifested as neuronal excitotoxicity, is involved in the aetiology of Alzheimer's disease. Targeting the glutamatergic system, specifically NMDA receptors, offers a novel approach to treatment in view of the limited efficacy of existing drugs targeting the cholinergic system.

Memantine is a low-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors. By binding to the NMDA receptor with a higher affinity than Mg2+ ions, memantine is able to inhibit the prolonged influx of Ca2+ ions which forms the basis of neuronal excitotoxicity. The low-affinity of memantine, however, preserves the physiological function of the receptor as it can still be activated by the relatively high concentrations of glutamate released following depolarisation of the presynaptic neuron.

Serotonergic (5-HT3 receptor)

Memantine acts as an uncompetitive antagonist at the 5HT3 receptor, with a potency similar to that for the NMDA receptor. The clinical significance of this serotonergic activity in the treatment of Alzheimer's disease is unknown.

Cholinergic (Nicotinic acetylcholine receptor)

Memantine acts as an uncompetetive antagonist at different neuronal nicotinic neuronal receptors (nAChRs) at potencies similar to the NMDA receptor. . It has been shown that the number of nicotinic receptors in the brain are reduced in Alzheimer's disease, even in the absence of a general decrease in the number of neurons, and nicotinic receptor agonists are viewed as interesting targets for anti-Alzheimer drugs.

Clinical use

Indications

Memantine is indicated for the treatment of the symptoms of moderate to severe Alzheimer's disease.

Memantine has been associated with a moderate decrease in clinical deterioration in Alzheimer's disease. A systematic review of randomised controlled trials found that memantine has a small positive effect on cognition, mood, behaviour, and the ability to perform daily activities in moderate to severe Alzheimer's disease, but an unknown effect in mild to moderate disease.

Memantine is also being tested for depression, glaucoma, tinnitus, neuropathic pain, and pervasive developmental disorders.

Adverse drug reactions

Memantine is generally well-tolerated. Common adverse drug reactions (≥1% of patients) include: confusion, dizziness, drowsiness, headache, insomnia, agitation, and/or hallucinations. Less common adverse effects include: vomiting, anxiety, hypertonia, cystitis, and increased libido.

© Medic8 ® All Rights Reserved.