Article: Memantine

Memantine
Systematic (IUPAC) name
1-amino-3,5-dimethyl-adamantane
Identifiers
CAS number	19982-08-2
ATC code	N06DX01
PubChem	4054
DrugBank	APRD00221
Chemical data
Formula	C12H21N
Mol. weight	179.3 g/mol
Pharmacokinetic data
Bioavailability	~100%
Metabolism	Hepatic (<10%)
Half life	60–100 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	B2 (Au), B (U.S.)
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Routes	Oral

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

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.^[1]

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.

5-HT₃

Memantine acts as an uncompetitive antagonist at the 5HT₃ receptor, with a potency similar to that for the NMDA receptor.^[2] The clinical significance of this serotonergic activity in the treatment of Alzheimer's disease is unknown.

Clinical use

Indications

Memantine is indicated for the treatment of the symptoms of moderate to severe Alzheimer's disease.^[3][4]

Memantine has been associated with a moderate decrease in clinical deterioration in Alzheimer's disease.^[4] 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.^[5]

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

Adverse drug reactions

Memantine is generally well-tolerated.^[5] 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.^[3][4]

See also

• Alzheimer's disease
• Donepezil
• Galantamine
• Rivastigmine