Memantine is an NMDA receptor antagonist used in the treatment of Alzheimer's disease. It differs from traditional agents used in Alzheimer's disease by acting on glutamatergic neurotransmission, rather than cholinergic. It is marketed by Lundbeck under the trade names Ebixa, Axura, and Namenda.
Pharmacology
There is some evidence that dysfunction of glutamatergic neurotransmission, manifested as neuronal excitotoxicity, is involved in the aetiology of Alzheimer's disease. (Cacabelos et al., 1999) As such, targeting the glutamatergic system, specifically NMDA receptors, was 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.
Clinical use
Indications
Memantine is indicated for the treatment of the symptoms of moderately severe to severe Alzheimer's disease. (Lundbeck, 2003) It has not been shown to slow or reverse the neurodegenerative processes of Alzheimer's disease.
The efficacy of memantine for this indication has been shown in several clinical trials. A systematic review of randomised controlled trials found that it has a positive effect on cognition, mood, behaviour, and the ability to perform daily activities. (Areosa et al., 2004)
Adverse drug reactions
Memantine is generally well-tolerated. (Areosa et al., 2004) Adverse drug reactions (ADRs) include: dizziness, confusion, headache, hallucinations, and tiredness; and less commonly: vomiting, anxiety, hypertonia , cystitis, and increased libido. (Joint Formulary Committee, 2004)
References
- Areosa SA, McShane R, Sherriff F (2004). Memantine for dementia. Cochrane Database Syst Rev 2004 (4), CD003154. (Medline abstract)
- Cacabelos R, Takeda M, Winblad B (1999). The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer's disease. Int J Geriatr Psychiatry 14 (1), 3-47.
- Joint Formulary Committee (2004). British National Formulary (BNF) (47 ed.). London: British Medical Association and the Royal Pharmaceutical Society of Great Britain. ISBN 0-85369-584-9
- Lundbeck Australia Pty Ltd (2003). Ebixa Approved Product Information (Australia). Baulkham Hills: Lundbeck