Memantine
Clinical data | |
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Trade names | Axura, Ebixa, Namenda, others[1] |
AHFS/Drugs.com | Monograph |
MedlinePlus | a604006 |
License data | |
Pregnancy category |
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Routes of administration | By mouth |
Drug class | NMDA receptor antagonist |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | ~100% |
Metabolism | Liver (<10%) |
Elimination half-life | 60–100 hours |
Excretion | Kidney |
Identifiers | |
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Memantine is a medication used to slow the progression of moderate-to-severe
Common side effects include headache, constipation, sleepiness, and dizziness.[4][5] Severe side effects may include blood clots, psychosis, and heart failure.[5] It is believed to work by acting on NMDA receptors, working as pore blockers of these ion channels.[4]
Memantine was approved for medical use in the United States in 2003.
Medical use
Alzheimer's disease and dementia
Memantine is used to treat moderate-to-severe Alzheimer's disease, especially for people who are intolerant of or have a contraindication to AChE (acetylcholinesterase) inhibitors.[8][9] One guideline recommends memantine or an AChE inhibitor be considered in people in the early-to-mid stage of dementia.[10]
Memantine has been associated with a modest improvement;[11] with small positive effects on cognition, mood, behavior, and the ability to perform daily activities in moderate-to-severe Alzheimer's disease.[12][13] There does not appear to be any benefit in mild disease.[14]
Memantine when added to
Psychiatry
Bipolar disorder
Memantine has been investigated as a possible augmentation strategy for depression in bipolar disorder but meta-analytic evidence does not support its clinical utility.[17]
Autism
Effects in autism are unclear.[18][19]
Radiation therapy
Memantine has been recommended for use by professional organization consensus to prevent neurocognitive decline after whole brain radiotherapy.[20]
Adverse effects
Memantine is, in general, well tolerated.
Like many other
Memantine appears to be generally well tolerated by children with
Pharmacology
Glutamate
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.[25]
Memantine is a low-affinity voltage-dependent
Memantine's antagonism on NMDA receptors has aroused interest in repurposing it for mental illnesses such as bipolar disorder,[17] considering the involvement of the glutamatergic system in the pathophysiology of mood disorders.[31]
Serotonin
Memantine acts as a non-competitive antagonist at the
Cholinergic
Memantine acts as a non-competitive antagonist at different neuronal
Dopamine
Memantine was shown in a study
Sigmaergic
Memantine acts as an agonist at the
History
Memantine was first synthesized and patented by Eli Lilly and Company in 1968 as an anti-diabetic agent, but it was ineffective at lowering blood sugar. Later it was discovered to have central nervous system (CNS) activity, and was developed by Merz for dementia in Germany; the NMDA activity was discovered after trials had already begun. Memantine was first marketed for dementia in Germany in 1989 under the name Axura.[40]
In the US, some CNS activities were discovered at
In 2000, Merz partnered with Forest to develop the drug for Alzheimer's disease in the U.S. under the name Namenda.[40]
In 2000, Merz partnered with Suntory for the Japanese market and with Lundbeck for other markets including Europe;[43] the drug was originally marketed by Lundbeck under the name Ebixa.[40]
Sales of the drug reached $1.8 billion for 2014.[44] The cost of Namenda was $269 to $489 a month in 2012.[45]
In February 2014, as the July 2015 patent expiration for memantine neared,
In December 2014, a judge granted New York State its request and issued an injunction, preventing Actavis from withdrawing the IR version until generic versions could launch. Actavis appealed and in May a panel of the
Society and culture
Recreational use
One preclinical study on monkeys showed that memantine was capable of inducing a PCP-like intoxication.[51] Because of its very long biological half-life, memantine was previously thought not to be recreational, although a few cases of sporadic recreational use have been described.[52]
A study examining self-reported use of memantine on the social network Reddit showed that the drug was used recreationally and as a nootropic, but also that it was misused in various illnesses as self-medication without strong scientific basis.[53]
Brand names
As of August 2017, memantine is marketed under many brand names worldwide including Abixa, Adaxor, Admed, Akatinol, Alceba, Alios, Almenta, Alois, Alzant, Alzer, Alzia, Alzinex, Alzixa, Alzmenda, Alzmex, Axura, Biomentin, Carrier, Cogito, Cognomem, Conexine, Cordure, Dantex, Demantin, Demax, Dementa, Dementexa, Ebitex, Ebixa, Emantin, Emaxin, Esmirtal, Eutebrol, Evy, Ezemantis, Fentina, Korint, Lemix, Lindex, Lindex, Lucidex, Manotin, Mantine, Mantomed, Marbodin, Mardewel, Marixino, Maruxa, Maxiram, Melanda, Memabix, Memamed, Memando, Memantin, Memantina, Memantine, Mémantine, Memantinol, Memantyn, Memanvitae, Memanxa, Memanzaks, Memary, Memax, Memexa, Memigmin, Memikare, Memogen, Memolan, Memorel, Memorix, Memotec, Memox, Memxa, Mentikline, Mentium, Mentixa, Merandex, Merital, Mexia, Mimetix, Mirvedol, Modualz, Morysa, Namenda, Nemdatine, Nemdatine, Nemedan, Neumantine, Neuro-K, Neuroplus, Noojerone, Polmatine, Prilben, Pronervon, Ravemantine, Talentum, Timantila, Tingreks, Tonibral, Tormoro, Valcoxia, Vilimen, Vivimex, Witgen, Xapimant, Ymana, Zalatine, Zemertinex, Zenmem, Zenmen, and Zimerz.[1]
It was also marketed in some countries as a combination drug with donepezil (memantine/donepezil) under the brand names Namzaric, Neuroplus Dual, and Tonibral MD.[1]
Research
Psychiatry
Memantine, in light of its NMDA receptor antagonism, has been repurposed as a possible adjunctive treatment for depressive episodes in subjects with bipolar disorder, considering the involvement of the glutamatergic system in the pathophysiology of bipolar illness.[31] However, evidence from meta-analyses showed that memantine was not significantly superior to placebo for bipolar depression.[17]
Parkinson's
A phase III clinical trial is studying the potential of memantine as disease modifying treatment for Parkinson's disease, to slow progression of the disease.[54]
References
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- ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
- ^ "Axura EPAR". European Medicines Agency (EMA). 17 May 2002. Retrieved 27 February 2024.
- ^ a b c d e "Memantine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 25 April 2019. Retrieved 3 March 2019.
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- ^ NICE review of technology appraisal guidance 111 January 18, 2011 Alzheimer's disease - donepezil, galantamine, rivastigmine and memantine (review): final appraisal determination Archived 21 March 2019 at the Wayback Machine
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- ^ "Dementia: assessment, management and support for people living with dementia and their carers". National Institute for Health and Care Excellence (NICE). 20 June 2018. Archived from the original on 12 August 2020. Retrieved 6 August 2020.
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- ^ "Memantine Ki values". PDSP Ki Database. UNC. Archived from the original on 30 July 2022. Retrieved 30 July 2022.
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- ^ "Pharms - Memantine (also Namenda) : Erowid Exp: Main Index". erowid.org. Archived from the original on 7 November 2018. Retrieved 7 November 2018.
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- ^ Delevett P (9 January 2000). "Cash is king, focus is queen". Silicon Valley Business Journal. Archived from the original on 5 February 2017. Retrieved 5 February 2017.
- ^ Staff (15 August 2000). "Lundbeck signs memantine licensing agreement for Merz+Co". The Pharma Letter. Archived from the original on 20 April 2016. Retrieved 6 April 2016.
- ^ "Namenda Sales Data". Drugs.com. February 2014. Archived from the original on 27 April 2019. Retrieved 23 January 2018.
- ^ "Evaluating Prescription Drugs Used to Treat: Alzheimer's Disease. Comparing Effectiveness, Safety, and Price" (PDF). Consumer Reports Health. May 2012. Archived (PDF) from the original on 5 September 2012. Retrieved 16 February 2015.
- ^ Pollack A (15 September 2014). "Forest Laboratories' Namenda Is Focus of Lawsuit". The New York Times. Archived from the original on 10 February 2018. Retrieved 24 August 2017.
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- ^ "Actavis Confirms Appeals Court Ruling Requiring Continued Distribution of Namenda IR". Actavis. 22 May 2015. Archived from the original on 18 November 2017. Retrieved 24 August 2017.
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Further reading
- Lipton SA (April 2005). "The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonism". Current Alzheimer Research. 2 (2): 155–165. PMID 15974913.