Alzheimer's
Memantine may revolutionize drug therapy in Alzheimer's Disease
By Akanksha, Staff Reporter
Jan 13, 2005, 20:42

NAMENDA(Memantine Hydrochloride)is the only NMDA-receptor antagonist for the treatment of moderate to severe Alzheimer's disease.

It is the normal levels of glutamate which is required to play an integral role in the neural pathways associated with learning and memory.In Alzheimer's disease, abnormal glutamatergic activity may cause neuronal toxicity and impair learning.

In patients with Alzheimer's disease, persistent and uncontrolled activation of NMDA receptors is believed to occur.
This sustained low-level activation of the receptors may contribute to the neurodegeneration observed in this disease.
Therefore, controlling NMDA-receptor-mediated glutamatergic neurotransmission appears to be an important step in alleviating the symptoms of Alzheimer's disease.

NAMENDA is the first of a new class of medications for Alzheimer's disease with a mechanism of action that is distinct from currently available therapies�
It is the only NMDA-receptor antagonist approved for the treatment of moderate to severe Alzheimer's disease.

Patients treated with NAMENDA have exhibited significantly less cognitive decline on the Severe Impairment Battery (SIB) total score versus placebo over the 28-week study period.

This benefit was evident with respect to:
attention
language
praxis
visuospatial ability
construction
memory

The effects of NAMENDA on cognition and functional ability were assessed in a randomized, multicenter, double-blind, parallel-group, placebo-controlled U.S. study investigating the efficacy of NAMENDA in 252 patients with moderate to severe Alzheimer's disease. Patients aged �� 50 years, with a Mini-Mental State Examination (MMSE) score of �� 3 to �� 14 points, were randomized to treatment with NAMENDA 10 mg BID or placebo BID for 28 weeks.

It was found that NAMENDA provides a significantly superior effect on cognition versus placebo.
It was also found that NAMENDA-treated patients demonstrate significantly higher functional ability versus placebo over time.

When given in combination with donepezil, NAMENDA resulted in sustained cognitive performance above baseline, compared with the progressive decline seen with donepezil plus placebo. Even though most patients had been taking the higher dose of donepezil (9.4 mg mean dose) for approximately 2 years, significant improvements were seen when donepezil was combined with NAMENDA.This benefit above baseline was sustained for 6 months.

Patients receiving combination therapy with NAMENDA plus donepezil demonstrated significant improvement in cognitive scores and significantly less decline in ADL scores, compared with patients receiving donepezil plus placebo over the 24-week study period. Patients receiving NAMENDA plus donepezil were significantly more likely to stay on therapy and complete the trial than patients receiving donepezil plus placebo.

Also that,coadministration of NAMENDA with donepezil does not affect the pharmacokinetics of either compound and does not affect anticholinesterase activity.

NAMENDA has been found to have a favorable side-effect profile.
When compared with placebo, NAMENDA monotherapy is not associated with a significantly different dropout rate due to adverse events (11.5% versus 10.1%, respectively). And a low incidence of gastrointestinal side effects has been observed with NAMENDA compared with placebo:
constipation 5.3% versus 3.0%;
diarrhea 4.3% versus 4.6%;
vomiting 3.0% versus 2.3%; and
nausea 2.3% versus 2.5%.

In a combination therapy study, significantly more patients receiving NAMENDA plus donepezil completed the trial compared with patients receiving donepezil plus placebo. Discontinuation due to adverse events was 7.4% in the NAMENDA plus donepezil group and 12.4 in the donepezil plus placebo group.

No clinically relevant differences between NAMENDA and placebo groups have been seen with respect to:

vital signs (including no orthostatic changes)
laboratory values
electrocardiogram values

However,NAMENDA is contraindicated in patients with known hypersensitivity to memantine HCl or any excipients used in the formulation.

The most common adverse events reported with NAMENDA versus placebo (>5% and higher than placebo) were dizziness, confusion, headache, and constipation.

In patients with severe renal impairment, the use of NAMENDA has not been systematically evaluated and is not recommended.


Considering the potential for multiple drug use in the elderly, drug-drug interaction can be important when treating Alzheimer's disease. NAMENDA undergoes minimal metabolism: 57% to 82% of the drug is excreted unchanged in the urine.

NAMENDA also produces minimal inhibition of CYP450 enzymes, and interactions between NAMENDA and drugs that are either metabolized by these enzymes or inhibitors of these enzymes are unlikely.

However,there is no evidence that NAMENDA prevents or slows neurodegeneration in patients with Alzheimer's disease.



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