Drug forecast: memantine, prototype of a new approach to treatment of dementia.
OBJECTIVE
To review the first clinically useful N-methyl-D-aspartate (NMDA) inhibitor for the treatment of dementia, memantine.


METHODS
A MEDLINE/PUBMED search was conducted to identify pertinent studies, case reports, letters, and reviews in the English language. All articles published from 1950 to March 2003 were reviewed. Additional references were obtained from the bibliographies of these articles.


METHODS
All studies evaluating any aspect of memantine in humans.


RESULTS
The excitatory amino acid neurotransmitter glutamate is felt to play a role in neuroinflammation and destruction of cholinergic neurons associated with dementia. Memantine is an NMDA receptor antagonist which partially blocks glutamatergic neurotransmission in the central nervous system (CNS). It is a selective, moderate affinity, noncompetitive receptor blocker that rapidly associates with and dissociates from the NMDA receptor. Memantine, that is usually dosed once or twice daily, is predominantly eliminated as unchanged drug via the renal route (renal clearance accounts for 90% of total body clearance). Use of memantine is associated with significant improvements in a number of cognitive, functional, and behavioral assessment scales used in the evaluation of cognition-enhancing drugs in dementia. Adverse effects of memantine are generally referable to the CNS and include depression, insomnia, akathisia, agitation, dizziness, drowsiness, restlessness, and hyperexcitability.


CONCLUSIONS
Although there is no cure for dementia, memantine may delay disease progression and improve functioning to a clinically significant extent. However, efficacy has not been consistent within trials and no comparative data with acetylcholinesterase inhibitors (AchEI) are available. In addition, there are no controlled data available regarding combination memantine-AchEI therapy. Further study data are awaited.
Guay
David R P
DR
Institute for the Study of Geriatric Pharmacotherapy, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA. guayx001@umn.edu