Drug Evaluation
A brief review of the
1. Introduction
2. Overview of
pharmacodynamic properties
3. Pharmacokinetic characteristics:
absorption and distribution
Expert Opin. Drug Metab. Toxicol. Downloaded from informahealthcare.com by RMIT University on 09/09/14
4. Metabolism and elimination
5. Food interactions
6. Drug interactions
7. Special populations
8. Safety and tolerability
9. Therapeutic use including
dosage and administration
10. Conclusion
11. Expert opinion
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10.1517/17425255.3.1.135 © 2007 Informa UK Ltd ISSN 1742-5255
pharmacologic and therapeutic
aspects of memantine in
Alzheimer’s disease
Frederick Schmitt†, Melody Ryan & Gregory Cooper
†University
of Kentucky, Sanders-Brown Center on Aging, 800 S. Limestone Street, Lexington,
KY 40536-0230, USA
The past decade has seen an increase in therapeutic options for Alzheimer’s
disease (AD) that target neurotransmitters, such as acetylcholine, and
research continues to target abnormal proteins in the AD brain. Recently,
glutamate excitotoxicity has also become a target for AD treatment with the
advent of memantine. Clinical trial data reviewed for memantine show good
tolerability, low side-effect profiles and a positive therapeutic impact in mod-
erate-to-severe AD, both as monotherapy and in conjunction with donepezil.
However, additional data suggest variable benefits in the mild stages of AD.
Furthermore, published reports support reduced dosing in patients with sig-
nificant renal disease. However, the opportunity to target a second mecha-
nism in the treatment of AD, thereby providing added symptomatic benefit,
appears to be a useful consideration for clinicians who treat this devastating
neurodegenerative disorder.
Keywords: Alzheimer's disease, clinical trials, dementia, excitotoxicity, glutamate, memantine
Expert Opin. Drug Metab. Toxicol. (2007) 3(1):135-141
1. Introduction
Alzheimer’s disease (AD) is a chronic, debilitating neurodegenerative disorder. It is
estimated that > 4 million individuals suffer from this illness in the US alone, with
numbers expected to rise dramatically in the coming decades. Approximately 10%
of all people aged > 65 years are afflicted with this condition. Despite the increasing
prevalence and importance of this disease, available treatments are limited. For the
past decade, the mainstays of treatment have been the acetylcholinesterase inhibitors
donepezil, rivastigmine and galantamine. These agents all afford a modest degree of
symptomatic benefit. They are based on the cholinergic hypothesis of AD, which
posits that the symptoms of this disease result, at least in part, from a deficiency in
the cholinergic system within the brain. However, over time, it has become clear
that additional pathways, neurotransmitter systems and biochemical processes also
play important roles in this disease. Key pathologic features of AD include changes
in amyloid precursor protein and tau protein [1-4] that lead to neuritic plaques and
neurofibrillary tangles.
Recent attention has focused on the role of excitotoxicity within the CNS. It has
been shown that excitatory neurotransmitters, such as glutamate, can serve both a
physiologic, as well as neurotoxic, role in the brain. Such a neurotoxic role has been
implicated in a number of neurologic conditions ranging from ischemic stroke and
status epilepticus to neurodegenerative illnesses, including Huntington’s disease and
AD [5]. This has led to interest in the development of compounds capable of modu-
lating activity at glutamate receptors and, thereby, potentially attenuating excito-
toxicity, given emerging evidence that neurodegenerative diseases such as AD result,
in part, from derangements in glutamate homeostasis [5-7].
135
 Memantine
Although a complete review of the glutamate hypothesis and
neurodegenerative disease (e.g., AD) is beyond the scope of this
review, other reviews have appeared in the literature regarding
glutamate and excitotoxicity [8,9]. However, some of the findings
that are relevant to glutamate toxicity, long-term potentiation
(LTP), β-amyloid toxicity and AD are briefly reviewed.
2. Overview of pharmacodynamic properties
Glutamate is the principal excitatory neurotransmitter within
the CNS, in which up to 40% of synapses are glutamatergic.
The NMDA receptor is a voltage-sensitive, glutamate-gated
Expert Opin. Drug Metab. Toxicol. Downloaded from informahealthcare.com by RMIT University on 09/09/14
ion channel that, when activated, allows entry of Ca2+ into the
neuron. Activation typically occurs only after depolarization
by other ionotropic glutamate receptors (AMPA and kainate).
At rest, the NMDA receptor channel is blocked by a magne-
sium ion. It is been postulated that chronic overactivity at the
NMDA receptor, allowing excessive calcium influx into the
cell, may play a role in the progression of AD. It is felt that
excessive calcium influx may result in synaptic or dendritic
damage, necrosis or apoptosis [10,11].
Memantine is a noncompetitive NMDA receptor anta-
gonist. It acts selectively at NMDA receptors, with no activity
at AMPA/kainate receptors. It binds at, or near, the magne-
For personal use only.
sium-binding site and thereby blocks Ca2+ entry into the cell
through the NMDA receptor at times of partial neuronal depo-
larization, but allows entry during full neuronal depolarization.
Memantine is dependent on prior activation of the NMDA
receptor by glutamate in order to access its binding site. There-
fore, the NMDA channel must be open in order for meman-
tine to gain access and exhibit its blocking activity [10,11].
Memantine can rapidly occupy its receptor site and can quickly
disassociate with the receptor. This property allows for normal
physiologic signal transmission during times of learning or
recall, along with inhibiting pathologic, tonic overactivation
[10]. Finally, memantine exhibits a low affinity for the NMDA
receptor (> 500 nmol/l), a characteristic that likely allows for its
good tolerability profile. Other NMDA antagonists, such as
ketamine and phencyclidine, have high receptor affinities
(< 100 nmol/l); therefore, they have had unacceptably high
rates of neurotoxicity and, at times, have induced a psycho-
sis-like state. It is felt that this difference in receptor affinity
accounts for the relative lack of toxicity with memantine, possi-
bly by allowing for more dynamic adjustments of this
compound to ongoing synaptic activity [11].
Memantine may have neuroprotective qualities, as seen in a
number of model systems, both in vivo and in vitro. Preven-
tion of NMDA- and glutamate-induced cell death has been
shown in a number of culture systems, including rat retinal
ganglion, cerebellar, cortical, mesencephalic and hippocampal
neurons. Interestingly, in other tissue culture experiments,
memantine reduced tau hyperphosphorylation [12] and
promoted non-amyloidogenic amyloid precursor protein
processing [11,13,14]. These effects may contribute to the
observed efficacy of memantine in patients with AD. Other
136 Expert Opin. Drug Metab. Toxicol. (2007) 3(1)
studies, for example, have shown reduced cell loss in in vivo
rat models with administration of memantine [11,15-17].
2.1 Glutamate, neurotoxicity and
long-term potentiation
Much of the hypothesized action of memantine hinges on
indications that glutamate excitotoxicity is involved in AD
and other dementing disorders [18,19]. In AD, the early obser-
vations that β-amyloid can reduce glial uptake of glutamate
[20] and enhance glutamate toxicity [21] support the concept of
excitotoxicity as a mechanism in this disease. NMDA recep-
tors and glutamate may also have another role through cellu-
lar mechanisms involving the promotion of calpain
degradation of the tau protein, leading to neuronal death [7].
The preclinical evidence for the effects of memantine is
summarized in detail by Danysz and Parsons [22] and, there-
fore, will not be repeated here. However, given the proposed
mechanism of action of this compound, a brief commentary
on LTP seems warranted. LTP is viewed as a cellular substrate
of memory and involves NMDA receptors and intracellular
calcium levels [23,24]. For example, animal studies suggest that
β-amyloid inhibits NMDA receptor-dependent LTP [25].
Work by Parsons and colleagues [26-29] has investigated LTP
blockades in different in vitro and in vivo animal models. This
work in the CA1 region of the hippocampus, using direct ago-
nists of NMDA receptors as well as decreased magnesium
concentration, reduced LTP. This ‘loss’ of LTP, however, is
reversed with memantine administration. These and other
observations have led to the hypothesis that memantine
blocks the tonic overactivation of the NMDA receptors in
AD, but allows the receptor (and LTP) to function in the
presence of a ‘relevant synaptic signal’ [22].
2.2 Clinical trials
Multiple large-scale, multisite, double-blind, placebo-control-
led trials have now been completed with memantine in people
with AD (for a review of clinical trial measures used in the eval-
uation of AD therapies see [30]). In a study of 252 individuals
with moderate-to-severe AD (Mini-Mental State Exam
[MMSE]: 3 – 14, Global Deterioration Scale: 5 – 6, Functional
Assessment Staging ≥ 6a), subjects were randomized to meman-
tine, titrating to 20 mg/day, or placebo. Subsequent analysis
favored the memantine-treated group on multiple measures
including the Alzheimer’s Disease Cooperative Study’s
(ADCS-ADL19) [31] measure of activities of daily living and the
Severe Impairment Battery (SIB) [32] as a measure of cognition.
Although the between-group difference in the global clinician
rating (CIBIC-Plus) did not reach significance by the
intent-to-treat analysis (p = 0.06), a significant difference favor-
ing the memantine-treated group was seen in the observed cases
analysis [33]. In addition, recently published results from this
clinical trial’s open-label extension [34] appear to support the
relative safety of this compound.
In a larger study, 403 moderate-to-severe AD (MMSE:
5 – 14) patients taking stable dosages of donepezil were

randomized to the addition of memantine, titrating to 10 mg
b.i.d., versus placebo [35]. In this study, significant
between-group differences favoring the memantine-treated
group were seen in the primary end point measures
ADCS-ADL19 and SIB. Significant differences were noted on
the secondary outcome measures, including the CIBIC-Plus,
Behavioural Rating Scale for Geriatric Patients (a measure of
patient dependence on the caregiver) and the Neuropsychiatric
Inventory (a measure of behavioral disturbances) [35].
Although both of the above trials involved only out-patients
with moderate-to-severe AD, many clinicians are faced with
patients who may be in a facility or who may have other types
Expert Opin. Drug Metab. Toxicol. Downloaded from informahealthcare.com by RMIT University on 09/09/14
of dementia. An earlier trial examined the efficacy of meman-
tine, titrated to a dosage of 10 mg once daily, in 166 nursing
home patients with dementia [36]. A subsequent reanalysis of
this study separated these patients into two subgroups based
on their modified Hachinski Ischaemia Scale (HIS) scores.
One group had risk factors for vascular dementia (VaD; HIS
score > 4) and the other with relatively ‘pure’ AD (HIS score
< 4) [37]. This reanalysis included 41 AD patients treated with
memantine and 38 AD patients treated with placebo. In this
study, significant between-group differences favoring the
memantine-treated group were seen on both a measure of glo-
bal change and behavior/dependency (Behavioural Rating
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Scale for Geriatric Patients) for both AD and VaD patient
groups, although the placebo/drug difference was numerically
larger for the AD group.
Other clinical trial data involving memantine as either
monotherapy or in combination with cholinesterase inhibi-
tors in milder stages of AD have appeared in publications and
in abstract form. Summaries of the unpublished trials, includ-
ing safety data from open-label extensions plus different titra-
tion and daily dosing schedules up to 20 mg (once daily) are
available on the Forest Laboratories clinical trials website [101].
Results of a single trial of memantine monotherapy
(20 mg/day) versus placebo in mild-to-moderate AD
(MMSE: 10 – 22) have recently been published [38]. In this
study, 403 subjects were randomized to memantine, titrating
to 10 mg b.i.d., versus placebo in a 24-week multi-center trial.
Significant differences favoring the memantine-treated group
were seen on both primary measures, the CIBIC-Plus and the
AD Assessment Scale (cognitive subscale or ADAScog, a meas-
ure of cognitive function). Benefit was also seen on the Neu-
ropsychiatric Inventory (a measure of behavioural
disturbance), although not on the ADCS-ADL23 (a measure
of activities of daily living). Treatment discontinuations due
to adverse events during the trial were 9.5% in the memantine
and 5.0% in the placebo arms [38].
A second trial in mild-to-moderate AD has also been
completed. This trial randomized 427 mildly impaired AD
patients (baseline MMSE mean: 17), who were already on
stable cholinesterase inhibitors (e.g., donepezil, galantamine,
rivastigmine) therapy for at least 3 months, to receive either
memantine or placebo for 24 weeks. Unlike the study that
combined memantine and donepezil in moderate-to-severe
Expert Opin. Drug Metab. Toxicol. (2007) 3(1)
Schmitt, Ryan & Cooper
AD, the results of this trial revealed no discernable differ-
ences due to the addition of memantine over placebo on
either of the primary clinical outcome measures (ADAScog or
CIBIC-Plus) or for secondary outcomes of daily living skills
or behavioral symptoms. Of importance, however, are the
safety data that also showed no differences in treat-
ment-emergent adverse events between the two groups [101].
Therefore, these data lend themselves to speculations regard-
ing the nature of AD neurotransmitter therapies based on
disease stage or progression, as well as the timing of different
types of therapy for AD. Additional data from the
open-label extensions of this trial, providing memantine for
up to 2 years, reveal the potential for slowing of AD pro-
gression (e.g., MMSE scores only declined by an average of
4.6 points over 104 weeks), but without placebo controls no
clear conclusions can be derived from these unpublished
data regarding maintenance of symptomatic effects much
less disease modification.
3.Pharmacokinetic characteristics:
absorption and distribution
Memantine is well absorbed following oral dosing with a bio-
availability of ∼ 100% [39]. Following a linear dose–concentra-
tion pattern [40], the maximum serum concentration is
achieved in 3 – 7 h, with food having no influence on the rate
or extent of absorption [102]. Steady-state serum memantine
concentrations after an oral daily dose of 20 mg are in the
range of 0.5 – 1.0 µM [41].
Memantine is not protein bound to a clinically significant
degree (45%) [103,104]. The relatively high volume of dis-
tribution (9 – 11 l/kg) demonstrates extensive distribution
throughout the body in the unionized state; memantine easily
diffuses across biological membranes [40]. Importantly,
memantine has been shown to cross the blood–brain barrier
and to distribute to many areas within the brain [40,41].
In an attempt to determine the specific brain distribution
of memantine, radiolabeled [18F]-memantine was adminis-
tered intravenously to five healthy volunteers. Positron emis-
sion tomography scans were obtained over a 2-h period.
During this time, the level of radioactivity in the brain tissues
continued to increase, but never attained a peak or plateau.
The amount of radioactivity in the brain tissue was dependent
on perfusion and possibly demonstrated nonspecific binding;
only slightly related to the regional NMDA receptor concen-
trations in the various brain areas [42]. Although this study
determined that radiolabeling of memantine is not helpful for
research purposes, it did demonstrate that memantine is
distributed to the brain.
A small, six-patient study demonstrated the achievement of
memantine cerebrospinal fluid (CSF) concentrations that
were linearly correlated with serum concentrations (R = 0.99,
p = 0.0018). The mean CSF/serum ratio was 0.52 ± 0.0904,
because only unbound memantine was available to cross the
blood–brain barrier [102].
137
 Memantine
4. Metabolism and elimination
Memantine does not undergo extensive metabolism, with
57 – 82% of dose eliminated unchanged in the urine [105].
Three memantine metabolites are formed: N-gludantan con-
jugate, 6-hydroxy memantine and 1-nitroso-deaminated
memantine. These metabolites have minimal NMDA recep-
tor activity [102]. The CYP enzyme system has little involve-
ment in the metabolism of mematine, thus, the potential for
drug–drug interactions is largely decreased [102]. The clearance
of memantine is ∼ 170 ml/min/1.73 m2. Clearance is reduced
in the elderly and in those with decreased creatinine clearance
Expert Opin. Drug Metab. Toxicol. Downloaded from informahealthcare.com by RMIT University on 09/09/14
(CrCl). The elimination half-life of memantine is 60 – 80 h
[105,106]. The correlation of memantine and CrCl emphasizes
the role of urinary elimination for this compound. Meman-
tine also undergoes renal tubular secretion and reabsorption
via cationic transport proteins. Because memantine is a weak
base (pKa = 10.27), there are possible concerns with changes
in the rate of elimination due to urine pH or urine flow
alterations [43].
To study the effects of variations in urine pH and urine flow
on memantine elimination, Freudenthaler et al. [43] designed a
crossover study. In this trial, 12 healthy males were randomized
to different sequences of the following groups: i) acidified
For personal use only.
urine pH and reduced urinary flow; ii) acidified urine pH and
increased urinary flow; iii) alkalinized urine pH and reduced
urinary flow; and iv) alkalinized urine pH and increased uri-
nary flow. Subjects were maintained at steady-state concentra-
tions of memantine and then were subjected to the altered
urinary state for a 1-day period. Each period was separated by
a wash-out phase. Alkalinization of the urine resulted in
decreased renal excretion and renal clearance, probably stem-
ming from reduced renal reabsorption. The renal clearance
decreased to a mean of 19.4 – 30.5 ml/min versus a mean of
148.6 ml/min without alterations. Acidification increased the
renal clearance to 223.3 – 234.3 ml/min [43]. Some patients
who may be taking memantine might undergo changes in
their urine pH as a result of medications or diet. Alkaline urine
conditions can be caused by a pure vegetarian diet and acidic
urine conditions can result from a very protein-rich diet [43]. In
this study, increasing urinary flow rate increased renal clear-
ance ∼ 9 ml/min. This increase was statistically significant, but
is unlikely to be clinically significant [43].
5. Food interactions
As noted above, absorption of oral memantine is not affected
by food. No significant interactions with food have been
reported [103].
6. Drug interactions
No in vitro [16] or in vivo [44] interactions with acetylcho-
linesterase inhibitors have been noted. Furthermore, in
healthy volunteers, the coadministration of memantine and
138 Expert Opin. Drug Metab. Toxicol. (2007) 3(1)
donepezil did not result in alterations of the pharmacokinetics
of either agent [44]. Memantine produces minimal inhibition
of CYP enzymes (CYP1A2, -2A6, -2C9, -2D6, -2E1 and
-3A4), suggesting a lack of interaction with other drugs
metabolized through this system [45]. Furthermore, although
memantine is predominantly excreted through the urine,
in vivo studies did not show a significant affect in AUC for
memantine after multiple doses of the diuretic hydrochloro-
thiazide/triamterene. Because of memantine’s low level of
plasma protein binding, any interaction with other highly
protein-bound medications, such as warfarin or digoxin, is
unlikely [103].
The combined use of memantine with other NMDA
antagonists (e.g., amantadine, ketamine, dextromethorphan)
has not been systematically studied. Therefore, caution is
urged when coadministering these agents [103].
7. Special populations
Caution is also recommended in individuals with moder-
ate-to-severe renal insufficiency, with dosing adjustments
made in patients with moderately reduced CrCl. Different
sources have different recommendations on the appropriate
use of memantine in renal insufficiency. The product infor-
mation provided by Forest Laboratories does not recommend
a dose reduction in moderate renal insufficiency, but does
recommend a decrease to 5 mg b.i.d. if CrCl is in the range of
5 – 29 ml/min [103]. The European Agency for Evaluation of
Medicinal Products suggest that memantine not be used in
severe renal insufficiency and that a dose reduction to 10 mg
once daily is used if CrCl is in the range of 40 – 60
ml/min/1.73m2 [106]. A recent report from Periclou et al. [45]
directly examined the impact of renal insufficiency on
memantine clearance. They enrolled 32 subjects in the age
range of 18 – 80 years (mean = 62.1, standard deviation [SD]
= 10.6) and subdivided these individuals based on CrCl into
four groups of eight subjects. Mean CrCl for the healthy and
mild groups were 93.5 (SD = 13.4) and 60.9 (SD = 7.9)
ml/min, respectively. Moderate impairment was in the range
of 50 – 75 ml/min (mean = 41.6, SD = 5.0) for eight subjects
and severe impairment was defined as 10 – 27 ml/min (mean
= 20.1, SD = 5.7) in the remaining eight. Subjects received a
single 20-mg oral dose of memantine followed by blood draws
and urine specimen collections (up to 504 h post-dose). Urine
samples were analysed for memantine plus its glucuronic acid
conjugate. Mean plasma concentrations were increased by
60% in the moderate and 115% in the severe impairment
groups compared with healthy controls. Elimination half-life
was increased by 95% in subjects with severe renal impair-
ment and 41% in moderately impaired subjects compared
with healthy subjects. Based on these data, Periclou et al. sim-
ulated the steady-state pharmacokinetic parameters across the
four renal groups. This simulation suggests that no change in
dosing (e.g., 10 mg b.i.d.) is needed in persons with mild or
moderate renal insufficiency. However, based on their

modeling, they recommend a reduction of dosing to 5 mg
b.i.d. in persons with severe renal impairment.
8. Safety and tolerability
Memantine has demonstrated an excellent safety and
tolerability profile. In a 12-week nursing home-based trial of
memantine versus placebo, adverse events were noted in 22%
of memantine-treated subjects compared with 21% of pla-
cebo-treated subjects [38]. In a 28-week study involving sub-
jects with moderate-to-severe AD, 84% of subjects receiving
memantine experienced an adverse event versus 87% of sub-
Expert Opin. Drug Metab. Toxicol. Downloaded from informahealthcare.com by RMIT University on 09/09/14
jects receiving placebo [33]. In patients with moder-
ate-to-severe AD already taking donepezil and, subsequently,
randomized to the addition of memantine versus placebo,
78% receiving memantine reported an adverse event versus
72% receiving placebo [35]. Most of these events were rated as
mild-to-moderate and unrelated to treatment. Discontinua-
tion in these trials was more common in placebo-treated sub-
jects. Similarly, in an integrated database of 587 patients with
dementia [102] serious adverse events were noted in 7% of
memantine recipients versus 10% of placebo recipients. Only
2% of memantine recipients versus 1% of placebo recipients
experienced serious adverse events considered possibly related
For personal use only.
to treatment.
Adverse events noted in ≥ 5% of subjects receiving meman-
tine with a greater than twofold incidence of that seen in sub-
jects receiving placebo includes confusion (8 versus 2%) [35],
somnolence (7 versus 1%) [44] and headache (6 versus 3%)
[34]. It should also be noted that a significantly lower incidence
of agitation as an adverse event has been noted in memantine
treated subjects versus placebo (18 versus 32%) [33].
Finally, no clinically significant abnormalities have been
noted on laboratory, electrocardiogram and vital sign
measurements [33,35].
9.Therapeutic use including dosage
and administration
Memantine has been approved for use in patients with mod-
erate-to-severe AD in both Europe and the US. Applications
for an expanded indication to include mild-to-moderate AD
were submitted, but not approved, in the US [107]. The
present recommended dosage is 20 mg/day divided into
twice-daily dosing. Although the long half-life of 60 – 80 h
would appear to support once-daily dosing, only one study
has used a once-daily regimen for dementia patients [37].
Other daily dosing and titration schemes have been studied in
open-label extension trials, but only safety data are available
on the Forest Laboratories website [101]. Higher daily doses of
memantine have been used in patients with phantom limb
Expert Opin. Drug Metab. Toxicol. (2007) 3(1)
Schmitt, Ryan & Cooper
pain (30 mg) [4], but no data with doses higher than
20 mg/day are available for dementia. Although these doses
might be safe, it is unknown if increased efficacy would result.
Dosing typically starts at 5 mg daily and increases at weekly
intervals to a target of 10 mg b.i.d. As noted above and based
on European Agency for the Evaluation of Medicinal Prod-
ucts guidelines, doses may be reduced for patients with mod-
erate renal insufficiency (CrCl: 40 – 60 ml/min/1.73m2) to
10 mg once daily [106]. If memantine use is desired in patients
with severe renal impairment (CrCl: 5 – 29 ml/min), the dose
should be reduced to 5 mg b.i.d.
10. Conclusion
Excitotoxicity has been hypothesized as an important mecha-
nism in the pathogenesis of AD. Memantine is a non-
competitive, low-affinity, voltage-dependent NMDA
receptor antagonist. It is thought to exert its activity by
blocking calcium influx into neurons during time of partial,
pathologic depolarization, and allowing normal receptor
channel functioning at times of full, physiologic neuronal
depolarization. Animal models suggest a potential for neuro-
protection, although this effect has not been confirmed in
human studies. Emerging evidence from a number of large,
multi-center, double-blinded, placebo-controlled clinical
trials demonstrate a clinical benefit [46] in the treatment of
moderate-to-severe AD either as monotherapy or add-on
therapy to a cholinesterase inhibitor.
11. Expert opinion
The introduction of memantine to the clinician’s armamen-
tarium for moderate-to-severe AD has had an impact on the
treatment of this devastating neurodegenerative disorder.
Although it has thus far been approved for only moder-
ate-to-severe disease, the clinical trial evidence is equivocal
regarding its efficacy in mild AD. Its use as add-on therapy
with the cholinesterase inhibitors is becoming commonplace,
and is supported by recent clinical trials in advanced AD.
Over time, the use of this compound may increase and its role
may grow in other related disorders, such as vascular dementia
and other neurodegenerative illnesses, if the glutamate excito-
toxicity hypothesis gains in strength. Perhaps, based on the
data involving animal models, we may also see trials of this or
similar agents that evaluate whether or not it serves a
neuroprotective role in addition to its symptomatic effects.
Conflicts of interest
This work was supported by National Institute on Aging
grants P50 AG05144 and R01 AG19241.
139
 Memantine
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=734345
TRIANO CE: Forest Laboratories
Announces FDA Decision on Supplemental
New Drug Application for Namenda®
(2005).
Affiliation
Frederick Schmitt†1, Melody Ryan2 &
Gregory Cooper3,4
†Author for correspondence
1University of Kentucky, Sanders-Brown Center
on Aging, and Department of Neurology, and
Departments of Psychiatry, Psychology, and
Behavioural Sciences, 800 S. Limestone Street,
Lexington, KY 40536-0230, USA
E-mail: fascom@email.uky.edu
2University of Kentucky, Department of
Neurology, and Department of Pharmacy
Practice and Science, 800 S. Limestone Street,
Lexington, KY 40536-0230, USA
3University of Kentucky, Sanders-Brown Center
on Aging, and Department of Neurology,
800 S. Limestone Street, Lexington, KY
40536-0230, USA
4Lexington Clinic, Division of Neurology,
Lexington, KY, USA
141