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Drugs & Aging
Published in: Drugs & Aging 6/2003

01-05-2003 | Adis Drug Profile

Memantine

Authors: Blair Jarvis, David P. Figgitt

Published in: Drugs & Aging | Issue 6/2003

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Abstract

  • ▲ Memantine, an uncompetitive antagonist with moderate affinity for NMDA receptors, demonstrates voltage-dependency and relatively fast on/off receptor kinetics.
  • ▲ Memantine 20 mg/day significantly slowed the rate of deterioration in outpatients with moderate to severe Alzheimer’s disease in a 28-week US randomised, double-blind, placebo-controlled, multicentre study.
  • ▲ Memantine 10 mg/day improved measures of dementia in care-dependent inpatients with Alzheimer’s disease or vascular dementia in a 12-week randomised, double-blind study. Significantly more memantine than placebo recipients were responders according to Clinical Global Impression of Change scores and the Behavioural Rating Scale for Geriatric Patients Care Dependence subscale.
  • ▲ Memantine 20 mg/day significantly improved cognition-related outcomes (cognitive subscale of the Alzheimer’s Disease Assessment Scale) in patients with vascular dementia in two 28-week randomised, double-blind, placebo-controlled, multicentre trials. No statistically significant between-group difference was seen in other primary endpoints.
  • ▲ Adverse events (incidence in memantine recipients greater than in placebo recipients) occurring in patients with moderately severe to severe dementia included diarrhoea, insomnia, dizziness, headache and hallucination.
Literature
1.
2.
3.
Erkinjuntti T. Cerebrovascular dementia: pathophysiology, diagnosis and treatment. CNS Drugs 1999 Jul; 12: 35–48CrossRef
4.
Cacabelos R, Takeda M, Winblad B. The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer’s disease. Int J Geriatr Psychiatry 1999; 14(1): 3–47PubMedCrossRef
5.
Fischer P-A, Jacobi P, Schneider E, et al. Effects of intravenous administration of memantine in Parkinsonian patients (in German]. Arzneimittelforschung 1977; 27(II) (7): 1487–9PubMed
6.
Ditzler K. Efficacy and tolerability of memantine in patients with dementia syndrome: a double-blind, placebo controlled trial. Arzneimittelforschung 1991 Aug; 41(8): 773–80PubMed
7.
Görtelmeyer R, Erbler H. Memantine in the treatment of mild to moderate dementia syndrome: a double-blind placebo-controlled study. Arzneimittelforschung 1992 Jul; 42(7): 904–13PubMed
8.
Pantev M, Ritter R, Görtelmeyer R. Clinical and behavioural evaluation in long-term care patients with mild to moderate dementia under memantine treatment. Zeitschrift Fur Gerontopsychologie Und -Psychiatrie 1993; 6: 103–17
9.
Grossmann W, Schütz W. Memantine and neurogenic bladder dysfunction in spastic conditions (in German). Arzneimittelforschung 1982; 32(II) (10): 1273–6PubMed
10.
Miltner FO. Use of symptomatic therapy with memantine in cerebral coma. I. Correlation of coma stages and EEG spectral patterns (in German). Arzneimittelforschung 1982; 32(10): 1268–70PubMed
11.
Winblad B, Möbius HJ, Stöffler A. Glutamate receptors as a target for Alzheimer’s disease — are clinical results supporting the hope? J Neural Transm 2002; 62 Suppl.: 217–25
12.
Doraiswamy PM. Non-cholinergic strategies for treating and preventing Alzheimer’s disease. CNS Drugs 2002; 16(12): 811–24PubMedCrossRef
13.
Ambrozi L, Danielczyk W. Treatment of impaired cerebral function in psychogeriatric patients with memantine — results of a phase II double-blind study. Pharmacopsychiatry 1988 May; 21(3): 144–6PubMedCrossRef
14.
Chen H-S, Pellegrini JW, Aggarwal SK, et al. Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. J Neurosci 1992 Nov; 12(11): 4427–36PubMed
15.
Chen H-S, Lipton SA. Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism. J Physiol 1997 Feb 15; 499 (Pt 1): 27–46PubMed
16.
Rohrbacher J, Bijak M, Misgeld U. Suppression by memantine and amantadine of synaptic excitation intrastriatally evoked in rat neostriatal slices. Neurosci Lett 1994 Nov 21; 182(1): 95–8PubMedCrossRef
17.
Parsons CG, Panchenko VA, Pinchenko VO, et al. Comparative patch-clamp studies with freshly dissociated rat hippocampal and striatal neurons on the NMDA receptor antagonistic effects of amantadine and memantine. Eur J Neurosci 1996 Mar; 8(3): 446–54PubMedCrossRef
18.
Frankiewicz T, Potier B, Bashir ZI, et al. Effects of memantine and MK-801 on NMDA-induced currents in cultured neurones and on synaptic transmission and LTP in area CA1 of rat hippocampal slices. Br J Pharmacol 1996 Feb; 117(4): 689–97PubMedCrossRef
19.
Sobolevsky AI, Koshelev SG, Khodorov BI. Interaction of memantine and amantadine with agonist-unbound NMDA-receptor channels in acutely isolated rat hippocampal neurons. J Physiol 1998 Oct 1; 512 (Pt 1): 47–60PubMedCrossRef
20.
Frankiewicz T, Parsons CG. Memantine restores long term potentiation impaired by tonic N-methyl-D-aspartate (NMDA) receptor activation following reduction of Mg2+ in hippocampal slices. Neuropharmacology 1999 Sep; 38(9): 1253–9PubMedCrossRef
21.
Blanpied TA, Boeckman FA, Aizenman E, et al. Trapping channel block of NMDA-activated responses by amantadine and memantine. J Neurophysiol 1997 Jan; 77(1): 309–23PubMed
22.
Bormann J. Memantine is a potent blocker of N-methyl-D-aspartate (NMDA) receptor channels. Eur J Pharmacol 1989 Aug 3; 166(3): 591–2PubMedCrossRef
23.
Parsons CG, Gruner R, Rozental J, et al. Patch clamp studies on the kinetics and selectivity of N-methyl-D-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan). Neuropharmacology 1993 Dec; 32(12): 1337–50PubMedCrossRef
24.
Krieglstein J, Lippert K, Pöch G. Apparent independent action of nimodipine and glutamate antagonists to protect cultured neurons against glutamate-induced damage. Neuropharmacology 1996; 35 (No. 12): 1737–42PubMedCrossRef
25.
Erdö SL, Schafer M. Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-D-aspartate. Eur J Pharmacol 1991 Jun 6; 198(2–3): 215–7PubMedCrossRef
26.
Weller M, Finiels-Marlier F, Paul SM. NMDA receptor-mediated glutamate toxicity of cultured cerebellar, cortical and mesencephalic neurons: neuroprotective properties of amantadine and memantine. Brain Res 1993; 613: 143–8PubMedCrossRef
27.
Pellegrini JW, Lipton SA. Delayed administration of memantine prevents N-methyl-D-aspartate receptor-mediated neurotoxicity. Ann Neurol 1993 Apr; 33(4): 403–7PubMedCrossRef
28.
Rammes G, Rupprecht R, Ferrari U, et al. 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 2001 Jun 22; 306(1–2): 81–4PubMedCrossRef
29.
Wenk GL, Zajaczkowski W, Danysz W. Neuroprotection of acetylcholinergic basal forebrain neurons by memantine and neurokinin B. Behav Brain Res 1997 Feb; 83(1–2): 129–33PubMedCrossRef
30.
Rao VLR, Dogan A, Todd KG, et al. Neuroprotection by memantine, a non-competitive NMDA receptor antagonist after traumatic brain injury in rats. Brain Res 2001 Aug 17; 911(1): 96–100PubMedCrossRef
31.
Görgülü A, Kins T, Çobanoglu S, et al. Reduction of edema and infarction by memantine and MK-801 after focal cerebral ischaemia and reperfusion in rat. Acta Neurochir (Wien) 2000; 142(11): 1287–92CrossRef
32.
Dogan A, Eras MA, Rao VLR, et al. Protective effects of memantine against ischemia-reperfusion injury in spontaneously hypertensive rats. Acta Neurochir (Wien) 1999; 141(10): 1107–13CrossRef
33.
Seif el Nasr M, Peruche B, Rossberg C, et al. Neuroprotective effect of memantine demonstrated in vivo and in vitro. Eur J Pharmacol 1990 Aug 21; 185(1): 19–24PubMedCrossRef
34.
Heim C, Sontag KH. Memantine prevents progressive functional neurodegeneration in rats. J Neural Transm 1995; 46 Suppl.: 117–30
35.
Stieg PE, Sathi S, Warach S, et al. Neuroprotection by the NMDA receptor-associated open-channel blocker memantine in a photothrombotic model of cerebral focal ischemia in neonatal rat. Eur J Pharmacol 1999 Jun 30; 375(1–3): 115–20PubMedCrossRef
36.
Keilhoff G, Wolf G. Memantine prevents quinolinic acid-induced hippocampal damage. Eur J Pharmacol 1992 Sep 4; 219(3): 451–4PubMedCrossRef
37.
Marvanová M, Lakso M, Pirhonen J, et al. The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain. Mol Cell Neurosci 2001 Sep; 18(3): 247–58PubMedCrossRef
38.
Schwenkreis P, Witscher K, Janssen F, et al. Influence of the N-methyl-D-aspartate antagonist memantine on human motor cortex excitability. Neurosci Lett 1999 Aug 6; 270(3): 137–40PubMedCrossRef
39.
Schugens MM, Egerter R, Daum I, et al. The NMDA antagonist memantine impairs classical eyeblink conditioning in humans. Neurosci Lett 1997 Mar 7; 224(1): 57–60PubMedCrossRef
40.
Schulz H, Jobert M, Coppola R, et al. The use of diurnal vigilance changes in the EEG to verify vigilance-enhancing effects of memantine in a clinical pharmacological study. Neuropsychobiology 1996; 33(1): 32–40PubMedCrossRef
41.
Rammsayer TH. Effects of pharmacologically induced changes in NMDA-receptor activity on long-term memory in humans. Learn Mem 2001; 8(1): 20–5PubMedCrossRef
42.
H. Lundbeck A/S. Summary of product characteristics. Ebixa (memantine hydrochloride). H. Lundbeck A/S, Valby, Denmark. 2002, 1–13
43.
Wenk GL, Quack G, Moebius HJ, et al. No interaction of memantine with acetylcholinesterase inhibitors approved for clinical use. Life Sci 2000 Feb 11; 66(12): 1079–83PubMedCrossRef
44.
Periclou A, Ventura D, Sherman T, et al. Pharmacokinetic study of memantine and donepezil in healthy young subjects [poster no. 32]. 26th Annual Meeting of the American Medical Directors Association; 2003 Mar 6–9; Orlando
45.
Reisberg B, Doody R, Stöffler A, et al. A randomized, placebo-controlled study of memantine, an uncompetitive NMDA antagonist, in patients with moderate to severe Alzheimer’s disease. N Engl J Med 2003; 348: 1333–41PubMedCrossRef
46.
Reisberg B, Möbius HJ, Stöffler A, et al. Long-term treatment with the NMDA antagonist memantine: results of a 24-week, open-label extension study in moderately severe to severe Alzheimer’s disease [abstract]. 8th International Conference on Alzheimer’s Disease and Related Disorders, Stockholm July 20–25 2000
47.
Ferris SH, Schmidt F, Doody R, et al. Long-term treatment with the NMDA antagonist, memantine: results of a 24-week, open-label extension study in advanced Alzheimer’s Disease [poster]. Annual Meeting of the American College of Neuropsychopharmacology, Waikoloa Village, Hawaii Dec 9–13 2001
48.
Winblad B, Poritis N. Memantine in severe dementia: results of the 9M-Best Study (benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry 1999 Feb; 14(2): 135–46PubMedCrossRef
49.
Orgogozo J-M, Rigaud A-S, Stöffler A, et al. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke 2002 Jul; 33(7): 1834–9PubMedCrossRef
50.
Wilcock G, Möbius HJ, Stöffler A. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol 2002 Nov; 17(6): 297–305PubMedCrossRef
51.
Farlow MR, Tariot PN, Grossberg GT, et al. Memantine/donepezil dual therapy is superior to placebo/donepezil therapy for treatment of moderate to severe Alzheimer’s disease [abstract no. 1035]. Neurology 2003; 60Suppl. 1: A412
52.
Wimo A, Winblad B, Stöffler A, et al. Resource utilisation and cost analysis of memantine in patients with moderate to severe Alzheimer’s disease. Pharmacoeconomics 2003; 21(5): 327–40PubMedCrossRef
53.
Wilcock G, Stoeffler A, Sahin K, et al. Neuro-radiological findings and the magnitude of cognitive benefit by memantine treatment: a subgroup analysis of two placebo-controlled clinical trials in vascular dementia [abstract]. Eur Neuropsychopharmacol 2000 Sep; 10Suppl. 3: S360CrossRef
54.
Hartmann S, Möbius HJ. Tolerability of memantine in combination with Cholinesterase inhibitors in dementia therapy. Int Clin Psychopharmacol 2003 Mar; 18(2): 81–5PubMedCrossRef
55.
Forest Laboratories. New study shows improved cognition relative to baseline for Alzheimer’s patients treated with investigational memantine and donepezil (Accessed 17 Dec 2002) [media release]. 2002
56.
Forest Laboratories. Forest Laboratories submits New Drug Application for investigational Alzheimer’s treatment memantine (Accessed 16 Apr 2002) [media release]. 2002
Metadata
Title
Memantine
Authors
Blair Jarvis
David P. Figgitt
Publication date
01-05-2003
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 6/2003
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.2165/00002512-200320060-00005

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