Antagonist memantine

Toggas SM, Masliah E, Mucke L (1996) Prevention of HIV-1 gpl20-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine. Brain Res 706 303-307... 

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]. 

The key to successful brain protection for Alzheimer s disease is the newly introduced NMDA receptor antagonist, memantine. Family members should be advised that the protection provided by memantine will slow the progression of Alzheimer s disease, but it does not halt or reverse the course of the illness. Memantine is now commonly coadministered with a cholinesterase inhibitor. 

In terms of clinical proof of neuroprotective effects in chronic neurodegenerative diseases, so far there are promising clinical results in ATS only with riluzole, and even then, the increase of survival obtained was only modest. The failure of r emacemide in a recent study in Huntington s disease was clearly a big setback. On the other hand, the moderate-affinity NMDA receptor antagonist memantine provides clear symptomatic improvement in dementia in both clinical and preclinical situations, and the precHnical data predict neuroprotective effects, substantiated by numerous animal models. 

Carlton SM, Hargett GL (1995) Treatment with the NMDA antagonist memantine attenuates nociceptive responses to mechanical stimulation in neuropathic rats. Netuosci Lett 198 115-118... 

Bisaga, A., Comer, S. D., Ward, A. S., Popik, P., Kleber, H., Fischman, M. W. The NMDA antagonist memantine attenuates the expression of opioid physical dependence in humans. Psychopharmacology 2001, 157, 1-10. 

Eisenberg, E., Kleiser, A., Dortort, A., Haim, T., Yarnitsky, D. The NMDA (N-methyl-D-aspartate) receptor antagonist memantine in the treatment of postherpetic neuralgia a double-blind, placebo-controlled study, Eur. J. Pain 1998, 2, 321-327. 

Paul C. and Bolton C. (2002). Modulation of blood-brain barrier dysfunction and neurological deficits during acute experimental allergic encephalomyelitis by the A-methyl-D-aspartate receptor antagonist memantine. J. Pharmacol. Exp. Ther. 302 50-57. 

Beister A, Kraus P, Kuhn W, Dose M, Weindl A, Gerlach M (2004) The N-methyl-D-aspartate antagonist memantine retards progression of Huntington s disease. J Neural Transm Suppl 117-122. 

It seems that altered intracellular calcium homeostasis may be a crucial event in the initiation and progression of AD however the therapeutic value has thus far been mixed. For example, the use of calcium channel blockers, including dihydropy-ridines and non-dihydropyridines, has no effect on the risk of AD (Yasar et al., 2005), whereas the NMDA-antagonist memantine improves cognition in mild to moderate AD (Peskind et al., 2006). 

Beister A, Kr aus P, Kulirr W, Dose M, Weindl A, Geriach M (2004) Tire N-metliyl-D-asparfate antagonist memantine retar ds progr es-sion of Himdng ton s disease. J Neiu al Transm Suppl 68 117—122. 

An alternative strategy for the treatment of AD is the use of the NMDA glutamate-receptor antagonist memantine (Namenda). 

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