化合物信息

Drug Groups

approved; investigational

Description

Memantine is an amantadine derivative with low to moderate-affinity for NMDA receptors. It is a noncompetitive NMDA receptor antagonist that binds preferentially to NMDA receptor-operated cation channels. It blocks the effects of excessive levels of glutamate that may lead to neuronal dysfunction. It is under investigation for the treatment of Alzheimer's disease, but there has been no clinical support for the prevention or slowing of disease progression.

Indication

For the treatment of moderate to severe dementia of the Alzheimer's type.

Pharmacology

Memantine, an amantadine derivative, 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. 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. A systematic review of randomised controlled trials found that memantine has a positive effect on cognition, mood, behaviour, and the ability to perform daily activities. There is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer's disease.

Toxicity

Side effects include pain, abnormal crying, leg pain, fever, increased apetite. Adverse drug reactions include: dizziness, confusion, headache, hallucinations, tiredness. Less common side effects include: vomiting, anxiety, hypertonia, cystitis, and increased libido. Doses of up to 400 mg have been tolerated.

Affected Organisms

Biotransformation

Excreted largely unchanged. About 20% is metabolized to 1-amino-3-hydroxymethyl-5-methyl-adamantane and 3-amino-1-hydroxy-5,7-dimethyl-adamantane.

Absorption

Well absorbed orally with a bioavailability of approximately 100%. Peak plasma concentrations are reached in 3-7 hours. Food has no effect on absorption.

Half Life

60-100 hours

Protein Binding

45%

Elimination

Memantine undergoes partial hepatic metabolism. About 48% of administered drug is excreted unchanged in urine; the remainder is converted primarily to three polar metabolites which possess minimal NMDA receptor antagonistic activity: the N-glucuronide conjugate, 6-hydroxy memantine, and 1-nitroso-deaminated memantine. It is excreted predominantly in the urine, unchanged.

Distribution

* 9 to 11 L/kg

References

External Links