NMDA receptor antagonists antagonist memantine

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). 

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... 

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. 

Memantine (Namenda) [Anti Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/ evere Alzheimer Dz Action N-methyl-D-aspartate recqjtor antagonist Dose Target 20 mg/d, start 5 mg/d, t 5 mg/d to 20 mg/d, wait >1 wk before t dose use doses if >5mg/d Caution [B, /-] Hqjatic/mild-mod renal impair Disp Tabs, sol SE Dizziness Interactions t Effects W amantadine, carbonic anhydrase inhibitors, dextromethorphan, ketamine, Na bicarbonate t effects W/ any drug, herb, food that alkalinizes urine EMS Use NaHCOs w/ caution OD May cause restlessness, hallucinations, drowsiness, and fainting symptomatic and supportive... 

It is beheved that phenomena such as sensitization, tolerance and drug-dependence might also involve synaptic plasticity. In fact, numerous studies indicate that NMDA receptor antagonists block sensitization to amphetamine and cocaine as well as tolerance and dependence to ethanol and opioids in animal models (Trujillo and Akil 1991 Pasternak and Inturrisi 1995 Trujillo and Akil 1995 Mao 1999). Recent studies indicate that the uncompetitive NMDA receptor antagonists dextromethorphan, memantine and neramexane not only prevent the development of morphine tolerance, but also reverse estabhshed tolerance in the continuing presence of this opioid, prevent the expression of withdrawal symptoms in rats (Popik and Skolnick 1996 Popik and Danysz 1997 Popik and Kozela 1999 Houghton et al. 2001) and attenuate the expres-... 

In humans, the antidepressant activity of NMDA receptor antagonists has not been evaluated extensively (Skohiick 1999). In animal models of depression, NMDA receptor antagonists have been reported to exert positive effects in most studies (Trullas 1997). This concerns mainly the forced swim test (Maj 1992 Moryl et al. 1993 PrzegaUnski et al. 1997) and stress-induced anhe-donia (Papp and Moryl 1994). Amantadine but not memantine was effective against reserpine-induced hypothermia (Moryl et al. 1993). In the forced swim test, both amino-adamantanes produced specific antidepressive-like activity (Moryl et al. 1993). 

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. 

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... 

Memantine is not a major substrate for hepatic cytochrome P450 isoenzymes and has not been shown to significantly inhibit or induce these enzymes. However, memantine is partially excreted by renal tubular secretion. Thus, concomitant use of other medications that use the same renal system (i.e., triampterene, hydrochlorothiazide, digoxin, cimetidine, ranitidine, metformin, and quinidine) may affect plasma levels of both drugs (Namenda 2005). Memantine should not be used in combination with other NMDA receptor antagonists, such as amantadine or dextromethorphan, because these combinations have not been formally studied. The clearance of memantine can be reduced when the urine is alkalinized, such as with the concomitant use of sodium bicarbonate or carbonic anhy-... 

Memantine (Namenda) [Anti-Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/severe Alzheimer Dz Action N-... 

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

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... 

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