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==Investigational use==
==Investigational use==
Memantine is also being tested for [[generalized anxiety disorder]], [[epilepsy]], [[opioid dependence]], [[systemic lupus erythematosus]], [[clinical depression|depression]], [[obsessive compulsive disorder]], [[Tourette Syndrome]], [[problem gambling]], [[attention-deficit hyperactivity disorder]] (ADHD),<ref>Open-Label Pilot Study of Namenda in Adult Subjects With ADHD and ADHD NOS [http://clinicaltrials.gov/ct2/show/NCT00586573?term=ADHD]</ref> [[glaucoma]], [[tinnitus]], [[neuropathy|neuropathic pain including Complex Regional Pain Syndrome]],<ref name="zeigler2">{{cite web |url=http://www.medforum.nl/idm/IDM1332001LA.pdf |title=New drugs to prevent or treat diabetic polyneuropathy|author=Dan Ziegler |accessdate=2008-01-07 |format= pdf|work=}} {{Dead link|date=September 2010|bot=H3llBot}}</ref> [[pervasive developmental disorder]]s, [[HIV associated dementia]],<ref>{{cite journal |author=Schifitto G, Navia BA, Yiannoutsos CT, ''et al.'' |title=Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study |journal=AIDS |volume=21 |issue=14 |pages=1877–86 |year=2007 |month=September |pmid=17721095 |doi=10.1097/QAD.0b013e32813384e8 }}</ref> [[pathologic nystagmus|nystagmus]],<ref>{{cite journal |author=Corbett J |title=Memantine/Gabapentin for the treatment of congenital nystagmus |journal=Curr Neurol Neurosci Rep |volume=7 |issue=5 |pages=395–6 |year=2007 |month=September |pmid=17764629 |doi=10.1007/s11910-007-0061-z }}</ref> [[multiple sclerosis]]<ref name="pmid19092106">{{cite journal |author=Villoslada P, Arrondo G, Sepulcre J, Alegre M, Artieda J |title=Memantine induces reversible neurologic impairment in patients with MS |journal=Neurology |volume= 72|issue= 19|pages= 1630–3|year=2008 |month=December |pmid=19092106 |doi=10.1212/01.wnl.0000342388.73185.80 |url=}}</ref>, [[autism]]<ref name="osumc">{{cite video | people=Aman, Michael (Interviewee) | date=2010-07-29 | url=http://www.youtube.com/watch?v=UZ2Rpm7syKY | title=Drug Used in Alzheimer's Tested In Kids With Autism | location=Ohio | publisher=Ohio State University Medical Center}}</ref> and [[migraine]].<ref>{{cite journal|last=Borghol|first=Amne|coauthors=Kirkwood A, Hawawini F|title=Memantine for the Treatment of Migraine|journal=US Pharm|date=May 2010|year=2010|volume=35|issue=5|pages=28–35|url=http://www.uspharmacist.com/content/c/20753/}}</ref>
Memantine is also being tested for [[generalized anxiety disorder]], [[epilepsy]], [[opioid dependence]], [[systemic lupus erythematosus]], [[clinical depression|depression]], [[obsessive compulsive disorder]], [[Tourette Syndrome]], [[problem gambling]], [[attention-deficit hyperactivity disorder]] (ADHD),<ref>Open-Label Pilot Study of Namenda in Adult Subjects With ADHD and ADHD NOS [http://clinicaltrials.gov/ct2/show/NCT00586573?term=ADHD]</ref> [[glaucoma]], [[tinnitus]], [[neuropathy|neuropathic pain including Complex Regional Pain Syndrome]],<ref name="zeigler2">{{cite web |url=http://www.medforum.nl/idm/IDM1332001LA.pdf |title=New drugs to prevent or treat diabetic polyneuropathy|author=Dan Ziegler |accessdate=2008-01-07 |format= pdf|work=}} {{Dead link|date=September 2010|bot=H3llBot}}</ref> [[pervasive developmental disorder]]s, [[HIV associated dementia]],<ref>{{cite journal |author=Schifitto G, Navia BA, Yiannoutsos CT, ''et al.'' |title=Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study |journal=AIDS |volume=21 |issue=14 |pages=1877–86 |year=2007 |month=September |pmid=17721095 |doi=10.1097/QAD.0b013e32813384e8 }}</ref> [[pathologic nystagmus|nystagmus]],<ref>{{cite journal |author=Corbett J |title=Memantine/Gabapentin for the treatment of congenital nystagmus |journal=Curr Neurol Neurosci Rep |volume=7 |issue=5 |pages=395–6 |year=2007 |month=September |pmid=17764629 |doi=10.1007/s11910-007-0061-z }}</ref> [[multiple sclerosis]]<ref name="pmid19092106">{{cite journal |author=Villoslada P, Arrondo G, Sepulcre J, Alegre M, Artieda J |title=Memantine induces reversible neurologic impairment in patients with MS |journal=Neurology |volume= 72|issue= 19|pages= 1630–3|year=2008 |month=December |pmid=19092106 |doi=10.1212/01.wnl.0000342388.73185.80 |url=}}</ref>, [[autism]]<ref name="osumc">{{cite video | people=Aman, Michael (Interviewee) | date=2010-07-29 | url=http://www.youtube.com/watch?v=UZ2Rpm7syKY | title=Drug Used in Alzheimer's Tested In Kids With Autism | location=Ohio | publisher=Ohio State University Medical Center}}</ref> and [[migraine]].<ref>{{cite journal|last=Borghol|first=Amne|coauthors=Kirkwood A, Hawawini F|title=Memantine for the Treatment of Migraine|journal=US Pharm|date=May 2010|year=2010|volume=35|issue=5|pages=28–35|url=http://www.uspharmacist.com/content/c/20753/}}</ref>

== Dosage ==

For immediate release, the initial dosage is one 5mg oral tablet per day. A dosage increase may be made after at least one week to 20mg Memantine per day. For extended release, the initial dosage is one 7 mg oral tablet per day. A dosage increase may be made after at least one week to 28mg Memantine per day.

Any dosage greater than 5mg per day must be given in two doses. Note: When switching from the intermediate release product to the extended release product, begin taking the extended release product the day after the last dose of the intermediate product.

For the off label use Vascular Dimentia, the dosage is initially one 5mg tablet once per day. It can be increased to a dose of one 10mg tablet twice daily.<ref>{{cite journal|last=Orgogozo|first=JM|coauthors=Rigaud AS, Stoffler A|title=Efficacy and Safety of Memantine in Patients with Mild to Moderate Vascular Dementia: A Randomized, Placebo-Controlled Trial (MMM 300)|journal=Stroke|year=2002|volume=33|pages=1834-39|url=http://0-www.ncbi.nlm.nih.gov.wildpac.wne.edu/pubmed/12105362?dopt=Abstract}}</ref>


== Adverse effects ==
== Adverse effects ==

Revision as of 18:22, 25 October 2011

Memantine
Clinical data
Trade namesNamenda
AHFS/Drugs.comMonograph
MedlinePlusa604006
License data
Pregnancy
category
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • S4 (Au), POM (UK), ℞-only (U.S.)
Pharmacokinetic data
Bioavailability~100%
MetabolismHepatic (<10%)
Elimination half-life60–100 hours
ExcretionRenal
Identifiers
  • 3,5-dimethyltricyclo[3.3.1.13,7]decan-1amine
    or
    3,5-dimethyladamantan-1-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.217.937 Edit this at Wikidata
Chemical and physical data
FormulaC12H21N
Molar mass179.3 g/mol g·mol−1
3D model (JSmol)
  • NC12CC3(CC(C1)(CC(C2)C3)C)C
  • InChI=1S/C12H21N/c1-10-3-9-4-11(2,6-10)8-12(13,5-9)7-10/h9H,3-8,13H2,1-2H3 checkY
  • Key:BUGYDGFZZOZRHP-UHFFFAOYSA-N checkY
  (verify)

Memantine is the first in a novel class of Alzheimer's disease medications acting on the glutamatergic system by blocking NMDA glutamate receptors. It was first synthesized by Eli Lilly and Company in 1968. Memantine is marketed under the brands Axura and Akatinol by Merz, Namenda by Forest, Ebixa and Abixa by Lundbeck and Memox by Unipharm. Despite years of research, whether memantine has any effect in mild to moderate Alzheimer's disease is unknown.[1]

Biochemistry

The drug belongs to a class of drugs called NMDA receptor antagonists, which help reduce abnormal activity in the brain by binding to NMDA receptors on brain cells and blocking the activity of the neurotransmitter glutamate. At normal levels, glutamate aids in memory and learning, but if levels are too high, glutamate appears to overstimulate nerve cells, killing off key brain cells.

Clinical use

Memantine is approved for treatment of moderate to severe Alzheimer's disease,[2] and has now received a limited recommendation by the UK's National Institute for Clinical Excellence for patients who fail other treatment options.[3] Within the new guidance memantine is recommended as an option for managing Alzheimer’s disease for people with: moderate Alzheimer’s disease who are intolerant of or have a contraindication to AChE (acetylcholinesterase) inhibitors or those with severe Alzheimer’s disease.

Memantine has been associated with a moderate decrease in clinical deterioration in Alzheimer's disease.[4] A systematic review of randomised controlled trials found that memantine has a small positive effect on cognition, mood, behaviour, and the ability to perform daily activities in moderate to severe Alzheimer's disease, but an unknown effect in mild to moderate disease.[1]


Memantine can help patients with severe Alzheimer's disease think more clearly and perform daily activities more easily, but, like other Alzheimer's drugs, it is not a cure and does not stop progression of the disease, the researchers[clarification needed] say.

Mild to moderate AD

As of April 2011 new research has emerged that shows this drug is not effective for treatment in stopping the progression of mild to moderate Alzheimers. In a review of 3 studies covering 431 patients with mild AD and 697 with moderate AD - there was no difference in the effectiveness of the drug Memantine. "There were no significant differences between memantine and placebo on any outcome for patients with mild AD, either within any trial or when data were combined," Dr. Lon Schneider of the University of Southern California and colleagues wrote in the Archives of Neurology. [5]

Greg M. Cole, a neuroscientist at the Greater Los Angeles VA Healthcare System and associate director of the Alzheimer's Disease Research Center at the University of California Los Angeles, said that "most of my clinician colleagues are not very impressed with the efficacy of memantine in mild to moderate Alzheimer's disease." Most researchers believe Alzheimer's disease has stages in which the responses to drugs differ, Cole said. "But this distinction is easily lost in the frustration of both lay persons and physicians who want to try whatever might help. So they try memantine in mild Alzheimer's disease cases," he said. "Some mild Alzheimer's disease patients might also respond, but until we can identify subsets of patients who respond well, we have to work with the average responses," Cole added. "Unfortunately, this new study demonstrates that the average response with mild to moderate Alzheimer's disease is marginal at best." [6]

Investigational use

Memantine is also being tested for generalized anxiety disorder, epilepsy, opioid dependence, systemic lupus erythematosus, depression, obsessive compulsive disorder, Tourette Syndrome, problem gambling, attention-deficit hyperactivity disorder (ADHD),[7] glaucoma, tinnitus, neuropathic pain including Complex Regional Pain Syndrome,[8] pervasive developmental disorders, HIV associated dementia,[9] nystagmus,[10] multiple sclerosis[11], autism[12] and migraine.[13]

Dosage

For immediate release, the initial dosage is one 5mg oral tablet per day. A dosage increase may be made after at least one week to 20mg Memantine per day. For extended release, the initial dosage is one 7 mg oral tablet per day. A dosage increase may be made after at least one week to 28mg Memantine per day.

Any dosage greater than 5mg per day must be given in two doses. Note: When switching from the intermediate release product to the extended release product, begin taking the extended release product the day after the last dose of the intermediate product.

For the off label use Vascular Dimentia, the dosage is initially one 5mg tablet once per day. It can be increased to a dose of one 10mg tablet twice daily.[14]

Adverse effects

Memantine is, in general, well-tolerated.[1] Common adverse drug reactions (≥1% of patients) include confusion, dizziness, drowsiness, headache, insomnia, agitation, and/or hallucinations. Less common adverse effects include vomiting, anxiety, hypertonia, cystitis, and increased libido.[4][15] It has been reported to induce reversible neurological impairment in multiple sclerosis patients, which led to the halt of an ongoing clinical trial.[11][16] Though exceedingly rare, extrapyramidal side-effects (such as dystonic reactions, etc.) may occur, in particular, in the younger population.[citation needed]

Pharmacology

Glutamatergic (NMDA receptor)

A dysfunction of glutamatergic neurotransmission, manifested as neuronal excitotoxicity, is hypothesized to be involved in the etiology of Alzheimer's disease. Targeting the glutamatergic system, specifically NMDA receptors, offers a novel approach to treatment in view of the limited efficacy of existing drugs targeting the cholinergic system.[17]

Memantine is a low-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors.[18][19][20] By binding to the NMDA receptor with a higher affinity than Mg2+ ions, memantine is able to inhibit the prolonged influx of Ca2+ ions, which forms the basis of neuronal excitotoxicity. The low affinity and rapid off-rate kinetics of memantine at the level of the NMDA receptor-channel, however, preserves the physiological function of the receptor, as it can still be activated by the relatively high concentrations of glutamate released following depolarization of the presynaptic neuron.[21][22][23][24][25][26][27][28] The interaction of memantine with NMDA receptors plays a major role in the symptomatic improvement that the drug produces in Alzheimer's disease. Moreover, there is no evidence as yet that the ability of memantine to protect against NMDA receptor-mediated excitotoxicity has a disease-modifying effect in Alzheimer's, although this has been suggested in animal models.[23]

Serotonergic (5-HT3 receptor)

Memantine acts as a non-competitive antagonist at the 5-HT3 receptor, with a potency similar to that for the NMDA receptor.[29] The clinical significance of this serotonergic activity in the treatment of Alzheimer's disease is unknown.

Cholinergic (nicotinic acetylcholine receptor)

Memantine acts as a non-competitive antagonist at different neuronal nicotinic acetylcholine receptors (nAChRs) at potencies possibly similar to the NMDA and 5-HT3 receptors, but this is difficult to ascertain with accuracy because of the rapid desensitization of nAChR responses in these experiments. It can be noted that memantine is an antagonist at alpha-7 nAChR, which may contribute to initial worsening of cognitive function during early memantine treatment. Alpha-7 nAChR upregulates quickly in response to antagonism, which could explain the cognitive-enhancing effects of chronic memantine treatment.[27][30][31] It has been shown that the number of nicotinic receptors in the brain are reduced in Alzheimer's disease, even in the absence of a general decrease in the number of neurons, and nicotinic receptor agonists are viewed as interesting targets for anti-Alzheimer drugs.[32] Consequently, this may also suggest that administration of nicotine itself may act against the effects of Alzheimer's disease.

Dopaminergic (D2 receptor)

Memantine acts as an agonist at the dopamine D2 receptor.[33]

History

Memantine was first synthesized and patented by Eli Lilly and Company in 1968 (as cited in the Merck Index), and then developed by Merz in collaboration with Neurobiological Technologies, Inc. and licensed to Forest for the U.S. and Lundbeck for selected European and international markets.

Sales of the drug reached $1.2 billion for 2010.

See also

References

  1. ^ a b c Areosa SA, Sherriff F, McShane R (2005). Areosa Sastre, Almudena (ed.). "Memantine for dementia". Cochrane Database Syst Rev (3): CD003154. doi:10.1002/14651858.CD003154.pub4. PMID 16034889.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Mount C, Downton C (2006). "Alzheimer disease: progress or profit?". Nat Med. 12 (7): 780–4. doi:10.1038/nm0706-780. PMID 16829947. {{cite journal}}: Unknown parameter |month= ignored (help)
  3. ^ NICE technology appraisal [1] Alzheimer's disease - donepezil, galantamine, rivastigmine and memantine (review): final appraisal determination, 18 Jan 2011
  4. ^ a b Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
  5. ^ "Common Alzheimer's Drug Found Ineffective". 12 April 2011.
  6. ^ "Drug Memantine Ineffective for Mild Alzheimer's, Study Finds". 11 April 2011.
  7. ^ Open-Label Pilot Study of Namenda in Adult Subjects With ADHD and ADHD NOS [2]
  8. ^ Dan Ziegler. "New drugs to prevent or treat diabetic polyneuropathy" (pdf). Retrieved 7 January 2008. [dead link]
  9. ^ Schifitto G, Navia BA, Yiannoutsos CT; et al. (2007). "Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study". AIDS. 21 (14): 1877–86. doi:10.1097/QAD.0b013e32813384e8. PMID 17721095. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Corbett J (2007). "Memantine/Gabapentin for the treatment of congenital nystagmus". Curr Neurol Neurosci Rep. 7 (5): 395–6. doi:10.1007/s11910-007-0061-z. PMID 17764629. {{cite journal}}: Unknown parameter |month= ignored (help)
  11. ^ a b Villoslada P, Arrondo G, Sepulcre J, Alegre M, Artieda J (2008). "Memantine induces reversible neurologic impairment in patients with MS". Neurology. 72 (19): 1630–3. doi:10.1212/01.wnl.0000342388.73185.80. PMID 19092106. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Aman, Michael (Interviewee) (29 July 2010). Drug Used in Alzheimer's Tested In Kids With Autism. Ohio: Ohio State University Medical Center.
  13. ^ Borghol, Amne (May 2010). "Memantine for the Treatment of Migraine". US Pharm. 35 (5): 28–35. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link)
  14. ^ Orgogozo, JM (2002). "Efficacy and Safety of Memantine in Patients with Mild to Moderate Vascular Dementia: A Randomized, Placebo-Controlled Trial (MMM 300)". Stroke. 33: 1834–39. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  15. ^ Joint Formulary Committee (2004). British National Formulary (47th ed.). London: BMA and the Royal Pharmaceutical Society of Great Britain. ISBN 0-85369-584-9.
  16. ^ Green AJ (2009). "Understanding pseudo. The symptoms are real, the cause is unclear". Neurology. 72 (19): 1626–7. doi:10.1212/01.wnl.0000345879.39454.68. PMID 19246422. {{cite journal}}: Unknown parameter |month= ignored (help)
  17. ^ Cacabelos R, Takeda M, Winblad B (1999). "The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer's disease". Int J Geriatr Psychiatry. 14 (1): 3–47. doi:10.1002/(SICI)1099-1166(199901)14:1<3::AID-GPS897>3.0.CO;2-7. PMID 10029935. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  18. ^ Kornhuber J, Bormann J, Retz W, Hübers M, Riederer P. Memantine displaces [3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur.J.Pharmacol. 166:589-590,1989. PMID 2680528
  19. ^ Rogawski, MA (2003). "The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease". CNS Drug Rev. 9 (3): 275–308. doi:10.1111/j.1527-3458.2003.tb00254.x. PMID 14530799. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  20. ^ Robinson, DM (2006). "Memantine: a review of its use in Alzheimer's disease". Drugs. 66 (11): 1515–34. doi:10.2165/00003495-200666110-00015. PMID 16906789. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  21. ^ Kornhuber J, Weller M. "Psychotogenicity and NMDA receptor antagonism: implications for neuroprotective pharmacotherapy". Biol.Psychiatry 41:135-144, 1997. PMID 9018383
  22. ^ Rogawski, MA (2000). "Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents—toward an understanding of their favorable tolerability". Amino Acids. 19 (1): 133–49. doi:10.1007/s007260070042. PMID 11026482. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help)
  23. ^ a b Parsons CG, Stöffler A, Danysz W (2007). "Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system — too little activation is bad, too much is even worse". Neuropharmacology. 53 (6): 699–723. doi:10.1016/j.neuropharm.2007.07.013. PMID 17904591. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  24. ^ Chen HS, Pellegrini JW, Aggarwal SK; et al. (1 November 1992). "Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity". J Neurosci. 12 (11): 4427–36. PMID 1432103. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  25. ^ Chen HS, Lipton SA (15 February 1997). "Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism". J Physiol. (Lond.). 499 (Pt 1): 27–46. PMC 1159335. PMID 9061638.
  26. ^ Lipton SA (2006). "Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond". Nat Rev Drug Discov. 5 (2): 160–70. doi:10.1038/nrd1958. PMID 16424917. {{cite journal}}: Unknown parameter |month= ignored (help)
  27. ^ a b Chen HS, Lipton SA (2006). "The chemical biology of clinically tolerated NMDA receptor antagonists". J Neurochem. 97 (6): 1611–26. doi:10.1111/j.1471-4159.2006.03991.x. PMID 16805772. {{cite journal}}: Unknown parameter |month= ignored (help)
  28. ^ Lipton SA (2007). "Pathologically activated therapeutics for neuroprotection". Nat Rev Neurosci. 8 (10): 803–8. doi:10.1038/nrn2229. PMID 17882256. {{cite journal}}: Unknown parameter |month= ignored (help)
  29. ^ Rammes G, Rupprecht R, Ferrari U, Zieglgänsberger W, Parsons CG (2001). "The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner". Neurosci Lett. 306 (1–2): 81–4. doi:10.1016/S0304-3940(01)01872-9. PMID 11403963. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  30. ^ Buisson B, Bertrand D (1 March 1998). "Open-channel blockers at the human alpha4beta2 neuronal nicotinic acetylcholine receptor". Mol Pharmacol. 53 (3): 555–63. PMID 9495824.
  31. ^ Aracava Y, Pereira EF, Maelicke A, Albuquerque EX (2005). "Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons". J Pharmacol Exp Ther. 312 (3): 1195–205. doi:10.1124/jpet.104.077172. PMID 15522999. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  32. ^ Gotti C, Clementi F (2004). "Neuronal nicotinic receptors: from structure to pathology". Prog Neurobiol. 74 (6): 363–96. doi:10.1016/j.pneurobio.2004.09.006. PMID 15649582. {{cite journal}}: Unknown parameter |month= ignored (help)
  33. ^ Seeman P, Caruso C, Lasaga M (2008). "Memantine agonist action at dopamine D2High receptors". Synapse. 62 (2): 149–53. doi:10.1002/syn.20472. PMID 18000814. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

Further reading

  • Lipton SA (2005). "The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonism". Current Alzheimer research. 2 (2): 155–65. doi:10.2174/1567205053585846. PMID 15974913.

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