Memantine in Alzheimer’s disease

Jones, R.W., McCrone, P., Gudhaume, C. (2004) Cost effectiveness of memantine in Alzheimer s disease an analysis based on a probabilistic Markov model from a U.K. perspective. Drugs Aging, 21, 607-620. 

Grossberg G. T., Edwards K. R., and Zhao Q. (2006). Rationale for combination therapy with galantamine and memantine in Alzheimer s disease. J. Clin. Pharmacol. 46 17S-26S. 

Schmitt F., Ryan M., and Cooper G. (2007). A brief review of the pharmacologic and therapeutic aspects of memantine in Alzheimer s disease. Expert Opin. Drug Metab Toxicol. 3 135-141. 

Schmitt F, Ryan M, Cooper G (2007) A brief review of the pharmacologic and therapeutic aspects of memantine in Alzheimer s disease. Expert Opin Drug Metab Toxicol 3 135-141 Schuster S, Nadjar A, Guo JT, Li Q, Ittrich C, Hengerer B, Bezard E (2008) The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor lovastatin reduces severity of L-DOPA-induced abnormal involuntary movements in experimental Parkinson s disease. J Neurosci 28 4311-4316... 

Even in Alzheimer s disease (AD), the possible involvement of a weak excitotoxic process cannot be ruled out. Indeed, mitochondrial abnormalities (such as cytochrome oxidase alterations) [36, 37] and increased levels of markers of oxidative stress [38] have been reported in AD. This has been the rationale for testing the NMDA antagonist memantine in Alzheimer s dementia [39]. 

Lipton, S.A. (2005). The molecular basis of memantine action in Alzheimer s disease and other neurologic disorders low-affinity uncompetitive antagonism. Curr. Alzheimer Res. 2 155-65. 

Kajitani K, Yrmagimoto K, Monji A, Maruyama T (2016) Memantine exacerbates corrected QT interval prolongation in Alzheimer s disease a case report from an unintentional rechallenge. J Am Geriatr Soc 64 232-233... 

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]. 

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. 

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. 

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 348( 14) 1333-41. 

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. 

Danysz W, Parsons CG, Mobius HJ, et al (2000) Neuroprotective and symptomatological action of memantine relevant for Alzheimer s disease—an unified glutamatergic hypothesis on the mechanism of action. Neurotox Res 2 85-97 Davis SM, Lees KR, Albers GW, et al (2000) Selfotel in acute ischemic stroke possible neurotoxic effects of an NMDA antagonist. Stroke 31 347-354 DeKeyser J (1991) Excitotoxic mechanisms may be involved in the pathophysiology of tardive dyskinesia. Clin Neuropharmacol 14 562-565 Del Dotto P, Pavese N, Gambaccini G, et al (2001) Intravenous amantadine improves levodopa-induced dyskinesias an acute double-blind placebo-controlled study. Mov Disord 16 515-520... 

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). 

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... 

Excitotoxic activation of glutamate transmission via NMDA receptors has been postulated to contribute to the pathophysiology of Alzheimer s disease. Memantine binds to NMDA receptor channels in a use-dependent manner and produces a noncompetitive blockade. This drug appears to be better tolerated and less toxic than the cholinesterase inhibitors. Memantine is available as Namenda in 5 and 10 mg oral tablets. 

Kirby J et al A systematic review of the clinical and cost-effectiveness of memantine in patients with moderately severe to severe Alzheimer s disease. Drugs Aging 2006 23 227. [PMID 16608378]... 

Q8 The drugs currently licensed for Alzheimer s disease in Britain are cholinesterase inhibitors, with one exception-memantine hydrochloride. This agent... 

Alzheimer s disease) and donepezil (79). These findings support the potential for combining memantine and cholinesterase inhibitors in patients with Alzheimer s disease. 

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