Glutamate receptor antagonists memantine

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

An alternative strategy for the treatment of AD is the use of the NMDA glutamate-receptor antagonist memantine (Namenda). Memantine produces a use-dependent blockade of NMDA receptors. In patients with moderate to severe AD, use of memantine is associated with a reduced rate of clinical deterioration. Whether this is due to a true diseasemodifying effect, possibly reduced excitotoxicity, or is a symptomatic effect of the drug is unclear. Adverse effects of memantine usually are mild and reversible, and may include headache or dizziness. 

Cosman KM, Boyle LL, Porsteinsson AP (2007) Memantine in the treatment of mUd-to-moderate Alzheimer s disease. Expert Opin Pharmacother 8 203-214 Draguhn A, Jahn W, Witzemann V (1991) Argiotoxin inhibits NMDA-activated ion channels expressed in Xenopus oocytes. Neurosci Lett 132 187-190 Eldefrawi AT, Eldefrawi ME, Konno K, Mansour NA, Nakanishi K, Oltz E, Usherwood PNR (1988) Structure and synthesis of a potent glutamate receptor antagonist in wasp venom. Proc Natl Acad Sd USA 85 4910-4913... 

Memantine is a non-competitive antagonist oftheN-methyl-D-aspartate (NMDA) type of glutamate receptors, which are located ubiquitously throughout the brain. It regulates activity... 

Pharmacology Persistent activation of CNS N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer disease. Memantine is an NMDA receptor antagonist. 

Parsons CG, Danysz W, Quack G (1998) Glutamate in CNS disorders as a target for drug development. An update. Drug News Perspect 11 523-569 Parsons CG, Danysz W, Quack G (1999) Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist—a review of preclinical data. Neuropharmacology 38 735-767... 

Of note, there have also been links between glutamate receptor stimulation and pathology. Excessive stimulation of glutamate receptors can cause seizure and it is hypothesized that NMDA overstimulation can cause neuronal cell death from an excessive influx of calcium. This has led to the development of NMDA antagonists like memantine to treat Alzheimer s Disease. 

Memantine hydrochloride, an NMDA receptor antagonist, reduces glutamate transmission and has shown beneficial effects. 

---