Drug Name: Namenda (memantine HCl)
Company: Forest Laboratories
Approval Status: Approved October 2003
Treatment for: Alzheimer's Disease

General Information
Namenda (Memantine) is an oral NMDA (N-methyl-D-aspartate) receptor antagonist. It appears to restore the function of damaged nerve cells and reduce abnormal excitatory signals. This is accomplished by the modulation of N-methyl-D-aspartate (NMDA) receptor activity.

Namenda is indicated for the treatment of moderate to severe dementia of the Alzheimer's type in adult patients.

The recommended starting dose of Namenda is 5 mg once daily. The recommended target dose is 20 mg/day.

The product was approved in Europe in May of 2002 for the Alzheimer's indication. There it is marketed there under the name Ebixa by Merz Pharmaceuticals.

Clinical Results
FDA approval of Namenda was based on two phase III, randomized, double-blind, placebo-controlled studies enrolling a total of 656 subjects with moderate to severe Alzheimer's disease. The average age of the study subjects was 76 ranging from 50 to 93 years old. Treatment efficacy was determined using both overall function through caregiver-related assessment, and an instrument that measures cognition. Day-to-day function was assessed in both studies using the modified Alzheimer's Disease cooperative Study --Activities of Daily Living inventory (ADCS-ADL). Results from both studies showed that that patients taking Namenda experienced significant improvement on both measures compared to placebo.

The first study enrolled 252 subjects with moderate to severe Alzheimer's disease who were administered Namenda (5 mg once daily and increased weekly by 5 mg/day) or placebo for 28-weeks. Results showed the mean difference in the ADCS-ADL change scores for Namenda compared with placebo was 3.4 units.

The second study enrolled 404 subjects with moderate to severe Alzheimer's disease who were administered Namenda (5 mg once daily and increased weekly by 5 mg/day) or placebo for 28-weeks. All Subjects had been treated with donepezil for at least 6 months and had been on a stable dose of donepezil for the last 3 months prior to the study. Results showed that the mean difference in the ADCS-ADL change scores for subjects treated with Namenda plus donepezil was 1.6 units compared with subjects treated with donepezil plus placebo.

Side Effects
Adverse events associated with the use of Namenda may include (but are not limited to) the following:

Fatigue
Pain
Hypertension
Headache
Constipation
Vomiting
Back pain
Somnolence

Mechanism of Action
Currently, all drugs approved for the treatment of Alzheimer's in U.S. belong to a class of drugs called acetylcholinesterase inhibitors. Namenda, a low to moderate affinity NMDA (N-methyl-D-aspartate) receptor antagonist is thought to selectively block the effects associated with abnormal transmission of the neurotransmitter glutamate, while allowing for the physiological transmission associated with normal cell functioning.

The overexcitation of NMDA receptors by the neurotransmitter glutamate may facilitate Alzheimer's disease since glutamate is found in the neural pathways associated with learning and memory. Abnormal levels of glutamate may be responsible for neuronal cell dysfunction and the eventual cell death observed in Alzheimer's disease.