Alzheimer Research Forum Overview of Namenda (memantine)

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Name: Memantine

Other Names: Ebixa™, Namenda™

Therapeutic Applications: cognition/memory enhancement

Therapy Types: pharmacological

Mechanisms: NMDA receptor antagonist

Development Status: approved in U.S.

FDA Phase: FDA approved

Primary Medical Role: Approved for the treatment of moderately severe to severe AD in EU in May 2002 and in US in October 2003.

Role in Alzheimer's Disease: Improves cognitive, social and motor impairment.

See Live Discussion:
Memantine: Implications for Treating Alzheimer's led by Steven T. DeKosky and Bengt Winblad.
http://www.alzforum.org/res/for/journal/dekosky/default.asp

Pharmacological Role: Excessive activation of N-methyl-D-aspartate (NMDA) receptors may underlie the degeneration of cholinergic cells. Memantine is a fast, voltage-dependent NMDA- receptor antagonist. It blocks the NMDA receptor in the presence of sustained release of low glutamate concentrations and thus attenuate NMDA receptor function.

Side Effects: The most frequently reported adverse events were dizziness (7%), headache(6%), and constipation(6%).

Evidence pro its efficacy: Two clinical trials showed 60-70% therapy response rate, with minimal side effects, in mild-to-moderate AD. A 28- week, multicenter clinical trial of patients with moderately severe to severe AD demonstrated a significant benefit of memantine over placebo on measures of overall function and cognition.

Dosage: Orally at a recommended dose of 10 mg BID following a four- week titration.

Companies: Merz + Co.

Notes: H. Lundbeck A/S holds marketing rights of memantine for certain European markets, Canada, Australia, and South Africa, and under the brand name Ebixa. Forest Laboratories, Inc. holds the rights to memantine for the U.S. market under the name Namenda; and Suntory, Ltd. for the Japan market. For more information on Memantine, see memantine.com and namemda.com.

References

Areosa SA, Sherriff F, McShane R. Memantine for dementia. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003154. Abstract

Livingston G, Katona C. The place of memantine in the treatment of Alzheimer's disease: a number needed to treat analysis. Int J Geriatr Psychiatry. 2004 Oct ;19(10):919- 25. Abstract

Periclou AP, Ventura D, Sherman T, Rao N, Abramowitz WT. Lack of Pharmacokinetic or Pharmacodynamic Interaction Between Memantine and Donepezil (September). Ann Pharmacother. 2004 Sep ; 38(9):1389-94. Abstract

Doody, R, Wirth, Y, Schmitt, F, Möbius, HJ. Specific Functional Effects of Memantine Treatment in Patients with Moderate to Severe Alzheimer's Disease. Dement Geriatr Cogn Disord. 2004 ; 18(2):227-32. Abstract

Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, . Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004 Jan 21;291(3):317- 24. Abstract

Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ. Memantine in moderate to severe Alzheimer's disease. N Engl J Med. 2003 Apr 3;348(14):1333-41. Abstract

Orgogozo JM, Rigaud AS, Stoffler A, Mobius HJ, Forette F. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo- controlled trial (MMM 300). Stroke. 2002 Jul;33(7):1834-9. Abstract

Dresser R. Weighing the benefits of new Alzheimer's treatments. Science. 2000 Aug 11;289(5481):869. Abstract

Marx J. Alzheimer's congress. Drug shows promise for advanced disease. Science. 2000 Jul 21;289(5478):375-7. Abstract

Wenk GL, Quack G, Moebius HJ, Danysz W. No interaction of memantine with acetylcholinesterase inhibitors approved for clinical use. Life Sci. 2000 Feb 11;66(12):1079-83. Abstract

Mobius HJ. Pharmacologic rationale for memantine in chronic cerebral hypoperfusion, especially vascular dementia. Alzheimer Dis Assoc Disord. 1999 Oct-Dec;13 Suppl 3:S172-8. Abstract

Parsons CG, Danysz W, Quack G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist--a review of preclinical data. Neuropharmacology. 1999 Jun;38(6):735-67. Abstract

Winblad B. Poritis N. Memantine in severe dementia: Results of the M-9-BEST study . International Journal of Geriatric Psychiatry. 1999 Feb;14(2):135-46. Abstract

Muller WE, Mutschler E, Riederer P. Noncompetitive NMDA receptor antagonists with fast open-channel blocking kinetics and strong voltage-dependency as potential therapeutic agents for Alzheimer's dementia. Pharmacopsychiatry. 1995 Jul;28(4):113-24. Abstract

Kornhuber J, Weller M, Schoppmeyer K, Riederer P. Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. J Neural Transm Suppl. 1994;43:91-104. Abstract

Ditzler K. Efficacy and tolerability of memantine in patients with dementia syndrome. A double-blind, placebo controlled trial. Arzneimittelforschung. 1991 Aug;41 (8):773-80. Abstract

Gortelmeyer R, Erbler H. Memantine in the treatment of mild to moderate dementia syndrome. A double-blind placebo- controlled study. Arzneimittelforschung. 1992 Jul;42 (7):904-13. Abstract

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