Alzheimer Treatments memantine

In pharmacology, two adamantane derivatives. Amantadine (1-adamanta-neamine hydrochloride) and Rimantadine (a-methyl-1-adamantane methyla-mine hydrochloride) (see Fig. 24), have been well known because of their antiviral activity [129]. The main application of these drugs is prophylaxis (treatment to prevent the onset of a particular disease) and treatment of influenza-A viral infections. They are also used in the treatment of parkinsonism and inhibition of hepatitis-C virus. Memantine (1-amino-3,5-dimethyladaman-tane) (see Fig. 24) has been reported effective in slowing the progression of Alzheimer s disease [130]. 

The ChE inhibitors all have the indication for the treatment of mild to moderate dementia of the Alzheimer s type. Guidelines for the treatment of AD were written before the approval of memantine and recommend the use of ChE inhibitors as a valuable treatment for AD.27-29 None of the ChE inhibitors have been compared in head-to-head studies, so the decision to use one over another is based on differences in mechanisms of action, adverse reactions, and titration schedules. 

Memantine is approved for treatment of moderate to severe Alzheimer s disease. It is an antagonist at glutamatergic NMDA-receptors. Memantine is well tolerated and has a small beneficial effect at six months in moderate to severe AD (McShane et al. 2006). For patients with dementia one has to be careful wit all kind of medications that may affect the central nervous system. Delirium and hallucinations are common adverse effects in patients with dementia. Agitation may be due to delirium and external causes should be ruled out before adding another psychoactive drug. Sleep disturbance is common in demented elderly patients. Sleep deprivation may in a patient with dementia induce delirium. Nonpharmacological treatment for delirium or hallucinations should be considered first. 

Alzheimer s Disease This disease is due to the accumulation of j8-amyloid protein in the brain. The protein is believed to trigger brain degeneration through cell death of the neurons. Alzheimer s disease is characterized by loss of memory and intellectual performance, and slowness in thought. In the United States, a class of drugs called cholinesterase inhibitors is approved to treat Alzheimer s disease. Both Europe and the United States have approved a drug called memantine for treatment of Alzheimer s disease. 

Ferris, S.H. (2003) Evaluation of memantine for the treatment of Alzheimer s disease. Expert Opin. Pharmacother., 4,2305-2313. 

Livingstone, G., Katona, C. (2004) The place of memantine in the treatment of Alzheimer s disease a number needed to treat analysis. Int. J. Geriatr. Psychiatry, 19, 919-925. 

Tariot PN, Farlow MR, Grossherg GT, Graham SM, McDonald S, Gergel I. Memantine treatment in patients with moderate to severe Alzheimer disease aheady receiving donepezU a randomized controlled trial. JAMA 2004 291(3) 317-24. 

Memantine is the first in a novel class of Alzheimer s disease medications acting a.o. on the NMDA receptor of the glutamatergic system. It also acts as an uncompetitive antagonist at different neuronal nicotinic receptors at potencies possibly similar to the NMDA receptor. Memantine is approved for treatment of moderate to severe Alzheimer s disease and its use is associated with a moderate decrease in clinical deterioration of the disease. Common adverse drug reactions (>1% of patients) include confusion, dizziness, drowsiness, headache, insomnia, agitation, and/or hallucinations. 

Geriatric Considerations - Summary Memantine is modestly effective for treatment of cognitive decline associated with moderate-to-severe Alzheimer s disease. Furthermore, for persons with moderate-to-severe AlzheimeFs disease using cholinesterase inhibitors, there is some evidence that memantine confers some additional benefit. Memantine is expensive, and its cost-effectiveness has not been demonstrated. Persons using drugs to treat Alzheimer s should be monitored closely, and prescribers should have a low threshold for discontinuing these agents if no clinical benefit is observed. 

Clinicians often use each cholinesterase inhibitor in combination with memantine however, the best evidence to date for such combination treatment is the use of memantine in patients with moderate to severe Alzheimer s disease already taking donepezil (Tariot et al. 2004). 

Memantine is currently the only medication approved by the FDA for the treatment of moderate to severe dementia of the Alzheimer s type (Reisberg et al. 2003 Winblad and Poritis 1999). Although its use also has been investigated in patients with mild to moderate vascular dementia (Orgogozo et al. 2002 Wilcock et al. 2002), this specific use has not yet been approved. 

Wilcock G, Mobius HJ, Stoffler A, et al A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol 17 297-305, 2002 Wilcock G, Howe 1, Coles H, et al A long-term comparison of galantamine and donepezil in the treatment of Alzheimer s disease. Drug Aging 20 777-789, 2003... 

Smith M., Wells J., and Borrie M. (2006). Treatment effect size of memantine therapy in Alzheimer disease and vascular dementia. Alzheimer Dis. Assoc. Disord. 20 133-137. 

A new class of medication, N-methyl-D-aspartate (NMDA)-receptor antagonist called memantine, was approved by the U.S. FDA and released in early 2004 under the brand name Namenda. It has been approved for the treatment of moderate to severe Alzheimer s disease and has been used in Germany for over 20 years. Clinical studies in the United States have shown modest effectiveness, with the main benefit being delayed deterioration of basic functions, such as the ability to go to the bathroom independently, feed oneself in a less messy fashion, be less easily distracted, and perhaps have less agitation. There is no evidence that it has any effect in the early stages of Alzheimer s disease or that it alters the ultimate course. Although these are modest benefits, they may allow a person to remain at home with family care and delay nursing-home placement for some period of time (Abramowicz, 2003). 

Autopsy studies on Alzheimer-afflicted brains some 40 years later showed a similar huge drop in neurotransmitter levels, but this time it was acetylcholine (ACh) in the hippocampus —which is associated with memory. Choline-esterase inhibitors, which stop the breakdown of ACh, were introduced and are presently the only symptom treatment available (Aricept, Excelon, Reminyl, Cognex). Recently, in 2004, memantine was approved as the first treatment to slow progression of Alzheimer s in mild to moderate cases. Work is ongoing to define acetylcholine-like muscarinic M-1 agonists and M-2 agonists that act on acetylcholine receptors directly. 

Doggrell S. Is memantine a breakthrough in the treatment ot moderate-to-severe Alzheimer s disease Expert Opin Pharmacother 2003 4 1857-60. 

Among promising candidates as antidotes against CNS intoxication by OP nerve agents, memantine (MEM) has been shown to pose both anti-excitotoxic and anti-epileptic properties. Memantine is an uncompetitive NMDA receptor antagonist, clinically used for the treatment of Alzheimer s disease, Parkinson s disease and spasticity, in the absence of serious side effects (Ozsuer et al, 2005 Lipton, 2005). From a series of rat in vivo experiments, it is evident that pre-administration of memantine significantly protects... 

Memantine is a competitive inhibitor of the A/-methyltaspar-tate glutamate receptor (NMDA). Clinically, memantine has been effective in the treatment of Alzheimer s dementia and... 

Parsons CG, Danysz W, Dekundy A, Pulte I (2013) Memantine and cholinesterase inhibitors Complementary mechanisms in the treatment of Alzheimer s disease. Neurotox Res 24 358-369... 

Yang Z, Zhou X, Zhang Q (2013) Effectiveness and safety of memantine treatment for Alzheimer s disease. J Alzheimers Dis 36 445-458... 

Besides the chohnesterase inhibitors, one of the current treatments available for the treatment of Alzheimer s disease is memantine. Since this chapter is devoted to chohnesterase inhibitors, discussion of memantine will only be in the context of its combination treatment with chohnesterase inhibitors. 

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