ممانتين

ممانتين
Memantine structure.svg
Memantine ball-and-stick model.png
البيانات السريرية
الأسماء التجاريةAxura, Ebixa, Namenda, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa604006
License data
فئة السلامة
أثناء الحمل
مسارات
الدواء		By mouth
رمز ATC
الحالة القانونية
الحالة القانونية
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
بيانات الحركية الدوائية
التوافر الحيوي~100%
الأيضLiver (<10%)
Elimination half-life60–100 hours
الإخراجKidney
المعرفات
رقم CAS
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.217.937 Edit this at Wikidata
Chemical and physical data
التركيبC12H21N
الكتلة المولية179.3 g/mol
3D model (JSmol)
  (verify)

ممانتين، is a medication used to treat moderate-to-severe Alzheimer's disease.[2][3] It is less preferred than acetylcholinesterase inhibitors such as donepezil.[3] Treatment should only be continued if beneficial effects are seen.[3] It is taken by mouth.[2]

Common side effects include headache, constipation, sleepiness, and dizziness.[2][3] Severe side effects may include blood clots, psychosis, and heart failure.[3] It is believed to work by blocking NMDA receptors.[2]

Memantine was approved for medical use in the United States in 2003.[2] It is available as a generic medication.[3] A month supply in the United Kingdom costs the NHS about 1.60 GBP as of 2019.[3] In the United States the wholesale cost of this amount is about US$5.50.[4] In 2016 it was the 147th most prescribed medication in the United States with more than 4 million prescriptions.[5]

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الاستخدام الطبي

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.[6][7] One guideline recommends memantine or an AChE inhibitor be considered in people in the early-to-mid stage of dementia.[8]

Memantine has been associated with a modest improvement;[9] with small positive effects on cognition, mood, behavior, and the ability to perform daily activities in moderate-to-severe Alzheimer's disease.[10][needs update][11] There does not appear to be any benefit in mild disease.[12]

While memantine can be used in combination with donepezil in those with dementia, the benefit of this is questionable and such dual use is not recommended by the National Institute of Clinical Excellence (NICE).[13] Memantine when added to donepezil in those with moderate to severe dementia resulted in "limited improvements" per a 2017 review.[14] Effects in autism are unclear.[15][16]


الآثار الجانبية

Memantine is, in general, well tolerated.[9] Common adverse drug reactions (≥1% of people) include confusion, dizziness, drowsiness, headache, insomnia, agitation, and/or hallucinations. Less common adverse effects include vomiting, anxiety, hypertonia, cystitis, and increased libido.[9][17]

Like many other NMDA antagonists, memantine behaves as a dissociative anesthetic at supratherapeutic doses.[18] Despite isolated reports, recreational use of memantine is rare due to the drug's long duration and limited availability.[18] Also memantine seems to lack effects such as euphoria or hallucinations.[19]

Memantine appears to be generally well tolerated by children with autism spectrum disorder.[20]

علم الأدوية

الگلوتامات

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.[21]

Memantine is a low-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors.[22][23] By binding to the NMDA receptor with a higher affinity than Mg2+ ions, memantine is able to inhibit the prolonged influx of Ca2+ ions, particularly from extrasynaptic receptors, which forms the basis of neuronal excitotoxicity. The low affinity, uncompetitive nature, and rapid off-rate kinetics of memantine at the level of the NMDA receptor-channel, however, preserves the function of the receptor at synapses, as it can still be activated by physiological release of glutamate following depolarization of the postsynaptic neuron.[24][25][26] The interaction of memantine with NMDA receptors plays a major role in the symptomatic improvement that the drug produces in Alzheimer's disease. However, 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.[25]

السروتونين

Memantine acts as a non-competitive antagonist at the 5-HT3 receptor, with a potency similar to that for the NMDA receptor.[27] Many 5-HT3 antagonists function as antiemetics, however the clinical significance of this serotonergic activity in the treatment of Alzheimer's disease is unknown.

الكولينيات

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.[28][29] 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.[30]

الدوپمين

Memantine acts as an agonist at the dopamine D2 receptor with equal or slightly higher affinity than to the NMDA receptors.[31]

مستقبلات سيگما

It acts as an agonist at the σ1 receptor with a low Ki of 2.6 μM (2600 nM).[32] The consequences of this activity are unclear (as the role of sigma receptors in general is not yet that well understood). Due to this low affinity, therapeutic concentrations of memantine are most likely too low to have any sigmaergic effect as a typical therapeutic dose is 20mg, however excessive doses of memantine taken for recreational purposes many times greater than prescribed doses may indeed activate this receptor.[33]

التاريخ

الأسماء التجارية

As of August 2017, memantine was 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, Xapimant, Ymana, Zalatine, Zemertinex, Zenmem, Zenmen, and Zimerz.[1]

It was also marketed in some countries as a combination drug with donepezil under the brands Namzaric, Neuroplus Dual, and Tonibral MD.[1]


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الأبحاث

In ADHD evidence is not sufficient to make any conclusions.[34] It has also been studied in migraines.[35]

المصادر

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  12. ^ Schneider LS, Dagerman KS, Higgins JP, McShane R (أغسطس 2011). "Lack of evidence for the efficacy of memantine in mild Alzheimer disease". Archives of Neurology. 68 (8): 991–8. doi:10.1001/archneurol.2011.69. PMID 21482915.
  13. ^ Hersen, Michel (2006). Comprehensive handbook of personality and psychopathology (Tertiary source). Hoboken, N.J: John Wiley. p. 514. ISBN 978-0-471-75725-2. OCLC 63041762.
  14. ^ Chen, Ruey; Chan, Pi-Tuan; Chu, Hsin; Lin, Yu-Cih; Chang, Pi-Chen; Chen, Chien-Yu; Chou, Kuei-Ru (21 أغسطس 2017). Chen, Kewei (ed.). "Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: A meta-analysis". PLOS ONE. 12 (8): e0183586. Bibcode:2017PLoSO..1283586C. doi:10.1371/journal.pone.0183586. ISSN 1932-6203. PMC 5565113. PMID 28827830.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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  19. ^ Swedberg MD, Ellgren M, Raboisson P (أبريل 2014). "mGluR5 antagonist-induced psychoactive properties: MTEP drug discrimination, a pharmacologically selective non-NMDA effect with apparent lack of reinforcing properties". The Journal of Pharmacology and Experimental Therapeutics. 349 (1): 155–64. doi:10.1124/jpet.113.211185. PMID 24472725.
  20. ^ Elbe, Dean (2019). Clinical handbook of psychotropic drugs for children and adolescents (Tertiary source). Boston, MA: Hogrefe. pp. 366–369. ISBN 978-1-61676-550-7. OCLC 1063705924.
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  25. ^ أ ب Parsons CG, Stöffler A, Danysz W (نوفمبر 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.
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  28. ^ Buisson B, Bertrand D (مارس 1998). "Open-channel blockers at the human alpha4beta2 neuronal nicotinic acetylcholine receptor". Molecular Pharmacology. 53 (3): 555–63. doi:10.1124/mol.53.3.555. PMID 9495824.
  29. ^ Aracava Y, Pereira EF, Maelicke A, Albuquerque EX (مارس 2005). "Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons". The Journal of Pharmacology and Experimental Therapeutics. 312 (3): 1195–205. doi:10.1124/jpet.104.077172. PMID 15522999.
  30. ^ Gotti C, Clementi F (ديسمبر 2004). "Neuronal nicotinic receptors: from structure to pathology". Progress in Neurobiology. 74 (6): 363–96. doi:10.1016/j.pneurobio.2004.09.006. PMID 15649582.
  31. ^ Seeman P, Caruso C, Lasaga M (فبراير 2008). "Memantine agonist action at dopamine D2High receptors". Synapse. 62 (2): 149–53. doi:10.1002/syn.20472. PMID 18000814.
  32. ^ Peeters M, Romieu P, Maurice T, Su TP, Maloteaux JM, Hermans E (أبريل 2004). "Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine". The European Journal of Neuroscience. 19 (8): 2212–20. doi:10.1111/j.0953-816X.2004.03297.x. PMID 15090047.
  33. ^ "Pharms - Memantine (also Namenda) : Erowid Exp: Main Index". erowid.org. Retrieved 7 نوفمبر 2018.
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  35. ^ Borghol A, Kirkwood A, Hawawini F (مايو 2010). "Memantine for the Treatment of Migraine". US Pharm. 35 (5): 28–35. This NMDA receptor antagonist, approved for the treatment of Alzheimer's disease, shows promise as a prophylactic therapy for these severe headaches

قراءات إضافية

  • Lipton SA (أبريل 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.

وصلات خارجية

قالب:Antidementia قالب:Antiparkinson

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