Memantine is a clinically well tolerated N-methyl-d-aspartate (NMDA) receptor antagonist—a review of preclinical data

Neuropharmacology - Tập 38 Số 6 - Trang 735-767 - 1999
Chris G. Parsons1, Wojciech Danysz1, G Quack1
1Department of Pharmacological Research, Merz and Co., Eckenheimer Landstrasse 100-104, D-60318 Frankfurt am Main, Germany

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Aisen, 1994, Inflammatory mechanisms in Alzheimer’s disease: implications for therapy, Am. J. Psychiatry, 151, 1105, 10.1176/ajp.151.8.1105

Andine, 1991, Changes in extracellular amino acids and spontaneous neuronal activity during ischaemia and extended reflow in the CA1 of the rat hippocampus, J. Neurochem., 57, 222, 10.1111/j.1471-4159.1991.tb02119.x

Andreassen, 1996, Inhibition by memantine of the development of persistent oral dyskinesias induced by long-term haloperidol treatment of rats, Br. J. Pharmacol., 119, 751, 10.1111/j.1476-5381.1996.tb15736.x

Apland, 1995, Anticonvulsant effects of memantine and (+)MK-801 in guinea pig hippocampal slices, Brain Res. Bull., 37, 311, 10.1016/0361-9230(95)00038-G

Auer, 1996, Postischemic therapy with (+)MK-801 (dizocilpine) in a primate model of transient focal brain ischemia, Mol. Chem. Neuropathol., 29, 193, 10.1007/BF02815002

Avenet, 1997, Antagonist properties of eliprodil and other NMDA receptor antagonists at rat NR1a/NR2A and NR1a/NR21B receptors expressed in Xenopus oocytes, Neurosci. Lett., 223, 133, 10.1016/S0304-3940(97)13422-X

Backhauss, 1992, A mouse model of focal cerebral ischemia for screening neuroprotective drug effects, J. Pharmacol. Toxicol. Meth., 27, 27, 10.1016/1056-8719(92)90017-U

Backhauss, 1992, Extract of Kava (Piper-Methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents, Eur. J. Pharmacol., 215, 265, 10.1016/0014-2999(92)90037-5

Barnes, 1996, Effects of the uncompetitive NMDA receptor antagonist memantine on hippocampal long-term potentiation, short-term exploratory modulation and spatial memory in awake, freely moving rats, Eur. J. Neurosci., 8, 565, 10.1111/j.1460-9568.1996.tb01241.x

Basile, 1996, N-methyl-d-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss, Nat. Med., 2, 1338, 10.1038/nm1296-1338

Beleslin, 1997, Opposite effects of GABA(A) and NMDA receptor antagonists on ethanol-induced behavioural sleep in rats, Alcohol, 14, 167, 10.1016/S0741-8329(96)00140-1

Belozertseva, I., Bespalov, A.Y. 1998. Effects of NMDA receptor channel blockers, dizocilpine and memantine, on the development of opiate analgesic tolerance induced by repeated morphine exposure or social defeats in mice Naunyn-Schmied. Arch. Pharmacol. 358, 270–274.

Benveniste, 1984, Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis, J. Neurochem., 43, 1369, 10.1111/j.1471-4159.1984.tb05396.x

Berger, 1996, Aminooxy-analogues of spermidine: new partial agonists and antagonists at the polyamine site of the rat hippocampal NMDA receptor complex, Neurosci. Lett., 203, 25, 10.1016/0304-3940(95)12255-9

Bienkowski, 1998, Study on the role of glycine, strychnine-insensitive receptors (glycineB sites) in the discriminative stimulus effects of ethanol in the rat, Alcohol, 15, 87, 10.1016/S0741-8329(97)00103-1

Birkmayer, 1975, The potentiation of the antiakinetic effect after l-DOPA treatment by an inhibitor of MAOB, deprenyl. J. Neural Transm., 36, 225

Bisaga, 1993, Effect of glutamate receptor antagonists on N-methyl-d-aspartate and (S)–a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced convulsant effects in mice and rats, Eur. J. Pharmacol., 242, 213, 10.1016/0014-2999(93)90244-C

Black, 1996, Study of potency, kinetics of block and toxicity of NMDA receptor antagonists using fura-2, Eur. J. Pharmacol., 317, 377, 10.1016/S0014-2999(96)00730-3

Blanpied, 1997, Trapping channel block of NMDA-activated responses by amantadine and memantine, J. Neurophysiol., 77, 309, 10.1152/jn.1997.77.1.309

Block, 1996, Memantine reduces functional and morphological consequences induced by global ischemia in rats, Neurosci. Lett., 208, 41, 10.1016/0304-3940(96)12545-3

Block, 1998, The b-wave of the electroretinogram as an index of retinal ischemia, Gen. Pharmacol., 30, 281, 10.1016/S0306-3623(97)00359-5

Bormann, 1989, Memantine is a potent blocker of N-methyl-d-aspartate (NMDA) receptor channels, Eur. J. Pharmacol., 166, 591, 10.1016/0014-2999(89)90385-3

Bormann, 1992, Induction of apoptosis by gp120 of HIV-1 in rat cortical cell cultures: prevention by memantine, Biol. Chem. Hoppeseyler, 372, 947

Braak, 1993, Staging of Alzheimer-related cortical destruction, Eur. Neurol., 33, 403, 10.1159/000116984

Bresink, 1996, Effects of memantine on recombinant rat NMDA receptors expressed in HEK 293 cells, Br. J. Pharmacol., 119, 195, 10.1111/j.1476-5381.1996.tb15971.x

Bresink, 1994, Effects of chronic treatment with memantine on NMDA receptors assessed with autoradiography, Eur. J. Pharm. Sci., 2, 138, 10.1016/0928-0987(94)90242-9

Bresink, 1995, Different binding affinities of NMDA receptor channel blockers in various brain regions—indication of NMDA receptor heterogeneity, Neuropharmacology, 34, 533, 10.1016/0028-3908(95)00017-Z

Bresink, 1995, Chronic treatment with the uncompetitive NMDA receptor antagonist memantine influences the polyamine and glycine binding sites of the NMDA receptor complex in aged rats (P-D-Section), J. Neural Transm., 10, 11, 10.1007/BF02256626

Bubser, 1992, Differential behavioural and neurochemical effects of competitive and non-competitive NMDA receptor antagonists in rats, Eur. J. Pharmacol., 229, 75, 10.1016/0014-2999(92)90288-F

Buchan, 1990, Do NMDA antagonists protect against cerebral ischemia: are clinical trials warranted?, Cereb. Brain Metab. Rev., 2, 1

Buisson, 1992, Striatal protection induced by lesioning the substantia-nigra of rats subjected to focal ischemia, J. Neurochem., 59, 1153, 10.1111/j.1471-4159.1992.tb08358.x

Buisson, 1998, Open-channel blockers at the human α4β2 neuronal nicotinic acetylcholine receptor, Mol. Pharmacol., 53, 555, 10.1124/mol.53.3.555

Butterworth, 1996, Neuroactive amino acids in hepatic encephalopathy, Metab. Brain Dis., 11, 165, 10.1007/BF02069503

Cadet, 1994, Free radical mechanisms in schizophrenia and tardive dyskinesia, Neurosci. Biobehav. Rev., 18, 457, 10.1016/0149-7634(94)90001-9

Carlsson, 1990, Interaction between glutamatergic and monoaminergic systems within the basal ganglia—implications for schizophrenia and Parkinson’s disease, Trends Neurosci., 13, 272, 10.1016/0166-2236(90)90108-M

Carlton, 1995, Treatment with the NMDA antagonist memantine attenuates nociceptive responses to mechanical stimulation in neuropathic rats, Neurosci. Lett., 198, 115, 10.1016/0304-3940(95)11980-B

Carlton, 1994, Behavioral and electrophysiological effects of memantine in a primate model of peripheral neuropathy, Soc. Neurosci. Abs., 20, 18

Carter, 1995, Antagonists of the NMDA receptor-channel complex and motor co-ordination, Life Sci., 57, 917, 10.1016/0024-3205(95)02027-G

Chaplan, 1997, Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve injury evoked allodynia in the rat, J. Pharmacol. Exp. Ther., 280, 829

Chen, 1991, Open-channel block of NMDA responses by the antiparkinson drug memantine, Soc. Neurosci. Abs., 17, 7

Chen, 1997, Mechanism of memantine block of NMDA-activated channels in rat retinal ganglion cells: uncompetitive antagonism, J. Physiol., 499, 27, 10.1113/jphysiol.1997.sp021909

Chen, 1992, Open-channel block of N-methyl-d-aspartate (NMDA) responses by memantine-therapeutic advantage against NMDA receptor-mediated neurotoxicity, J. Neurosci., 12, 4427, 10.1523/JNEUROSCI.12-11-04427.1992

Chen, 1998, Neuroprotective concentrations of the N-methyl-d-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation, Neuroscience, 86, 1121, 10.1016/S0306-4522(98)00163-8

Chojnacka-Wojcik, 1983, The influence of memantine on the anticonvulsant effects of the antiepileptic drugs, Pol. J. Pharmacol. Pharm., 35, 511

Clement, 1995, In vivo studies on the effects of memantine on dopamine metabolism in the striatum and n. accumbens of the rat (Gen. Sect.), J. Neural Transm., 46, 107

Clements, 1992, The time course of glutamate in the synaptic cleft, Science, 258, 1498, 10.1126/science.1359647

Coan, 1989, Low-frequency activation of the NMDA receptor system can prevent the induction of LTP, Neurosci. Lett., 105, 205, 10.1016/0304-3940(89)90038-4

Coderre, 1993, The role of excitatory amino acid receptors and intracellular messengers in persistent nociception after tissue injury in rats, Mol. Neurobiol., 7, 229, 10.1007/BF02769177

Collingridge, 1990, Excitatory amino acid receptors and synaptic plasticity, Trends Pharmacol. Sci., 11, 290, 10.1016/0165-6147(90)90011-V

Costall, 1975, Neuropharmacological studies on D145 (1,3-dimethyl-5-aminoadamantan), Psychopharmacologia, 43, 53, 10.1007/BF00437615

Costall, 1975, Neuroleptic antagonism of dyskinetic phenomena, Eur. J. Pharmacol., 33, 301, 10.1016/0014-2999(75)90174-0

Costall, 1975, The 6-hydroxydopamine rotational model for the detection of dopamine agonist activity: reliability of effect from different locations of 6-hydroxydopamine, J. Pharm. Pharmacol., 279, 943, 10.1111/j.2042-7158.1975.tb10253.x

Czuczwar, 1996, Interactions of excitatory amino acid antagonists with conventional antiepileptic drugs, Metab. Brain Dis., 11, 143, 10.1007/BF02069501

Danysz, 1994, Glutamate antagonists have different effects on spontaneous locomotor activity in rats, Pharmacol. Biochem. Behav., 48, 111, 10.1016/0091-3057(94)90506-1

Danysz, 1994, Are NMDA antagonistic properties relevant for antiparkinsonian-like activity in rats? Case of amantadine and memantine (P-D-Section), J. Neural Transm., 7, 155, 10.1007/BF02253435

Danysz, 1995, Glutamate in CNS disorders: a revived target for drug development?, Drug News Perspect., 8, 261

Danysz, 1997, Aminoadamantanes as NMDA receptor antagonists and antiparkinsonian agents-preclinical studies, Neurosci. Biobehav. Rev., 21, 455, 10.1016/S0149-7634(96)00037-1

Danysz, 1995, Modulation of learning processes by ionotropic glutamate receptor ligands, Behav. Pharmacol., 6, 455, 10.1097/00008877-199508000-00007

Davidson, 1998, Intraplantar injection of dextrorphan, ketamine or memantine attenuates formalin-induced behaviors, Brain Res., 785, 136, 10.1016/S0006-8993(97)01396-6

Davies, 1988, Differences in results from in vivo and in vitro studies on the use-dependency of N-methylaspartate antagonism by MK-801 and other phencyclidine receptor ligands, Eur. J. Pharmacol., 145, 141, 10.1016/0014-2999(88)90225-7

Dekeyser, 1991, Excitotoxic mechanisms may be involved in the pathophysiology of tardive dyskinesia, Clin. Neuropharmacol., 14, 562, 10.1097/00002826-199112000-00009

Deshpande, 1995, Assessment of primary neuronal culture as a model for soman induced neurotoxicity and effectiveness of memantine as a neuroprotective drug, Arch. Toxicol., 69, 384, 10.1007/s002040050188

Deutsch, 1997, The antiseizure efficacies of MK-801, phencyclidine, ketamine, and memantine are altered selectively by stress, Pharmacol. Biochem. Behav., 58, 709, 10.1016/S0091-3057(97)90014-9

Dickenson, 1990, A cure for wind up: NMDA receptor antagonists as potential analgesics, Trends Pharmacol. Sci., 11, 307, 10.1016/0165-6147(90)90228-Z

Dimpfel, 1995, Effects of memantine on synaptic transmission in the hippocampus in vitro, Arzneim. Forsch. Drug Res., 45, 1

Dimpfel, 1987, Radioelectroencephalographic comparison of memantine with receptor-specific drugs acting on dopaminergic transmission in freely moving rats, Neuropsychobiology, 18, 212, 10.1159/000118420

Ditzler, 1991, Efficacy and tolerability of memantine in patients with dementia syndrome. A double-blind, placebo controlled trial, Arzneim. Forsch. Drug Res., 41, 773

Dreyer, 1995, The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid, Eur. J. Neurosci., 7, 2502, 10.1111/j.1460-9568.1995.tb01048.x

Dunn, 1986, Pharmacological activity of amantadine: effect of N-alkyl substitution, J. Pharm. Pharmacol., 38, 353, 10.1111/j.2042-7158.1986.tb04586.x

Ehrenberger, 1995, Receptor pharmacological models for inner ear therapies with emphasis on glutamate receptors: a survey, Acta Oto. Laryngol., 115, 236, 10.3109/00016489509139299

Eisenberg, 1994, The effects of the clinically tested NMDA receptor antagonist memantine on carrageenan-induced thermal hyperalgesia in rats, Eur. J. Pharmacol., 255, 123, 10.1016/0014-2999(94)90090-6

Eisenberg, 1995, The clinically tested N-methyl-d-aspartate receptor antagonist memantine blocks and reverses thermal hyperalgesia in a rat model of painful mononeuropathy, Neurosci. Lett., 187, 17, 10.1016/0304-3940(95)11326-R

Eisenberg, 1993, The NMDA antagonist memantine blocks pain behaviour in a rat model of formalin-induced facial pain, Pain, 54, 301, 10.1016/0304-3959(93)90029-O

Erdõ, 1991, Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-d-aspartate, Eur. J. Pharmacol., 198, 215, 10.1016/0014-2999(91)90625-Z

Farkas, 1988, Electrophysiologic measurement of the flexor reflex in cats for testing centrally acting muscle relaxant drugs, Pharmacol. Res. Comm., 20, 141, 10.1016/S0031-6989(88)80681-7

Fauman, 1981, Chronic phencyclidine (PCP) abuse: a psychiatric perspective, 419

Feilling, 1973, The effect of adding amantadine to optimum l-DOPA dosage in Parkinson’s syndrome, Acta Neurol. Scand., 49, 245, 10.1111/j.1600-0404.1973.tb01296.x

Ferger, 1996, Determination of intracellular Ca2+ concentration can be a useful tool to predict neuronal damage and neuroprotective properties of drugs, Brain Res., 732, 87, 10.1016/0006-8993(96)00494-5

Ferrer-Montiel, 1998, Structural determinants of the blocker binding site in glutamate and NMDA receptor channels, Neuropharmacology, 37, 139, 10.1016/S0028-3908(98)00007-0

Fisher, 1997, Evidence that glutamate regulates dopamine synthesis via aromatic l-amino acid decarboxylase, Br. J. Pharmacol., 120, 239P

Fisher, 1998, Differential effects of NMDA and non-NMDA antagonists on the activity of aromatic l-amino acid decarboxylase activity in the nigrostriatal dopamine pathway of the rat, Brain Res., 792, 126, 10.1016/S0006-8993(98)00129-2

Fix, 1995, Quantitative analysis of factors influencing neuronal necrosis induced by MK-801 in the rat posterior cingulate/retrosplenial cortex, Brain Res., 696, 194, 10.1016/0006-8993(95)00842-E

Frankiewicz, 1998, Effects of NMDA-receptor antagonists on long-term potentiation and hypoxic/hypoglycaemic excitotoxicity in hippocampal slices, Soc. Neurosci. Abs. 12, 24, 179

Frankiewicz, T., Parsons, C.G. Memantine restores long term potentiation impaired by tonic NMDA receptor activation following reduction of Mg2+ in hippocampal slices. Neuropharmacology, (submitted).

Frankiewicz, 1996, 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., 117, 689, 10.1111/j.1476-5381.1996.tb15245.x

Frey, 1991, Effect of pschotropic agents on a model of absence epilepsy in rats, Neuropharmacology, 30, 651, 10.1016/0028-3908(91)90086-Q

Fünfgeld, 1985, Experience with memantine in treatment of extrapyramidal and pyramidal movement disorders, Med. Klin., 80, 559

Gelbard, 1994, Platelet-activating factor: a candidate human immunodeficiency virus type-1-induced neurotoxin, J. Virol., 68, 4628, 10.1128/JVI.68.7.4628-4635.1994

Gerzon, 1963, The adamantyl group in medicinal agents. I. Hypoglycemic N-arylsulfonyl-N′-adamantylureas, J. Med. Chem., 6, 760, 10.1021/jm00342a029

Globus, 1991, Comparative effect of transient global ischemia on extracellular levels of glutamate, glycine, and gamma-aminobutyric acid in vulnerable and nonvulnerable brain regions in the rat, J. Neurochem., 57, 470, 10.1111/j.1471-4159.1991.tb03775.x

Globus, 1991, Excitotoxic index-a biochemical marker of selective vulnerability, Neurosci. Lett., 127, 39, 10.1016/0304-3940(91)90889-2

Görtelmeyer, 1992, Memantine in the treatment of mild to moderate dementia syndrome-a double-blind placebo-controlled study, Arzneim. Forsch. Drug Res., 42, 904

Görtelmeyer, 1993, The treatment of dementia syndrome with akatinol memantine, a modulator of the glutamatergic system, 50

Grabowska, 1975, Influence of dopamine-like compounds on stereotypy and locomotor activity in atropinized rats, Arch. Imm. Ther. Exp., 23, 753

Grabowska, 1976, The involvement of serotonin in the mechanism of central action of apomorphine, Pol. J. Pharmacol. Pharm., 28, 389

Grant, 1996, Dizocilpine-like discriminative stimulus effects of low-affinity uncompetitive NMDA antagonists, Neuropharmacology, 35, 1709, 10.1016/S0028-3908(96)00147-5

Greenamyre, 1988, Glutamate transmission and toxicity in Alzheimer’s disease, Prog. Neuro-Psych. Biol. Psych., 12, 421, 10.1016/0278-5846(88)90102-9

Greenamyre, 1992, N-methyl-d-aspartate antagonists in the treatment of Parkinson’s disease, Arch. Neurol., 48, 977, 10.1001/archneur.1991.00530210109030

Grimwood, 1996, Modulation of 45Ca2+ influx into cells stably expressing recombinant human NMDA receptors by ligands acting at distinct recognition sites, J. Neurochem., 66, 2589, 10.1046/j.1471-4159.1996.66062589.x

Grossmann, 1976, The effect of dimethylaminoadamantane on neuronal membranes, Eur. J. Pharmacol., 35, 379, 10.1016/0014-2999(76)90241-7

Grossmann, 1977, The effect of memantine (dimethylaminoadamantane) on membranes of sensory nerve fibers, Arzneim. Forsch. Drug Res., 27, 1483

Grossmann, 1982, Memantine and neurogenic bladder dysfunction in spastic conditions, Arzneim. Forsch. Drug Res., 32, 1273

Gunne, 1993, An animal model for coexisting tardive dyskinesia and tardive parkinsonism: a glutamate hypothesis for tardive dyskinesia, Clin. Neuropharmacol., 16, 90, 10.1097/00002826-199302000-00012

Gupta, 1992, Potential of memantine, d-tubocurarine, and atropine in preventing acute toxic myopathy induced by organophosphate nerve agents-soman, sarin, tabun and VX, Neurotoxicology, 13, 649

Gupta, 1993, Protection and reversal by memantine and atropine of carbofuran-induced changes in biomarkers, Drug Develop. Res., 28, 153, 10.1002/ddr.430280205

Gupta, 1989, Prevention and antagonism of acute carbofuran intoxication by memantine and atropine, J. Toxicol. Environ. Health, 28, 111, 10.1080/15287398909531332

Gupta, 1990, Methyl parathion acute toxicity: prophylaxis and therapy with memantine and atropine, Arch. Int. Pharmacod. Ther., 305, 208

Gupta, 1991, Subacute toxicity of aldicarb-prevention and treatment with memantine and atropine, Drug Develop. Res., 24, 343, 10.1002/ddr.430240405

Haacke, 1977, Induction of the platelet release reaction by 1.3-dimethyl-5-aminoadamantane, a new adamantane derivative, Thromb. Haemost., 37, 62, 10.1055/s-0038-1649202

Haacke, 1977, The mode of action of 1 aminoadamantanes. Comparative investigations with isolated nerve endings and blood platelets on the release of serotonin and dopamine, Arzneim. Forsch. Drug Res., 27, 1481

Hardin Pouzet, 1997, Glutamate metabolism is down-regulated in astrocytes during experimental allergic encephalomyelitis, Glia, 20, 79, 10.1002/(SICI)1098-1136(199705)20:1<79::AID-GLIA8>3.0.CO;2-0

Heim, 1995, Memantine prevents progressive functional neurodegeneration in rats, J. Neural Transm. Gen. Sect., 46, 117

Henkel, 1982, Structure-anti-Parkinson activity relationships in the aminoadamantanes. Influence of bridgehead substitution, J. Med. Chem., 25, 51, 10.1021/jm00343a010

Herrero, 1994, Memantine selectively depresses NMDA receptor mediated responses of rat spinal neurones in vivo, Neurosci. Lett., 165, 37, 10.1016/0304-3940(94)90703-X

Hesselink, 1997, Pharmacokinetic characterisation of two distinct classes of NMDA receptor antagonists using brain microdialysis, Soc. Neurosci. Abst., 23, 921

Hesselink, M.B., Smolders, H., De Boer, A.G., Breimer, D.D., Danysz, W., 1999a. Modifications of the behavioural profile of uncompetitive NMDA receptor antagonists, memantine, amantadine and (+)MK-801 after chronic administration. Behav. Pharmacol. 10, 85–98.

Hesselink, M.B., De Boer, A.G., Breimer, D.D., Danysz, W. 1999b. Brain penetration and in vivo recovery of NMDA receptor antagonists amantadine and memantine: a quantitative microdialysis study. Pharmaceut. Res. (in press).

Hölter, 1996, Evidence for alcohol anti-craving properties of memantine, Eur. J. Pharmacol., 314, R1, 10.1016/S0014-2999(96)00670-X

Honegger, 1993, Evidence for lysosomotropism of memantine in cultured human cells-cellular kinetics and effects of memantine on phospholipid content and composition, membrane fluidity and beta-adrenergic transmission, Pharmacol. Toxicol., 73, 202, 10.1111/j.1600-0773.1993.tb01564.x

Huber, 1997, Lack of neuronal vacuolation and necrosis in monkeys treated with Selfotel (CGS 19755.), a competitive N-methyl-d-aspartate receptor antagonists, Int. J. Toxicol., 16, 175, 10.1080/109158197227260

Hundt, 1998, Ethanol and N-methyl-d-aspartate receptor complex interactions: A detailed drug discrimination study in the rat, Psychopharmacology, 135, 44, 10.1007/s002130050484

Izumi, 1992, Low concentrations of N-methyl-d-aspartate inhibit the induction of long-term potentiation in rat hippocampal slices, Neurosci. Lett., 137, 245, 10.1016/0304-3940(92)90414-3

Jackisch, 1992, Studies on the mechanism of action of the antiparkinsonian drugs memantine and amantadine: no evidence for direct dopaminomimetic or antimuscarinic properties, Arch. Int. Pharmacod. Ther., 320, 21

Janiec, 1978, The effect of drugs stimulating central dopaminergic system on transformation of exogenous adenine into c-AMP, Pol. J. Pharmacol. Pharm., 30, 529

Janiec, 1977, The effect of apomorphine, amantadine and dimethylaminoadamantane on the level of cyclic AMP in the rat striatum, Pol. J. Pharmacol. Pharm., 29, 93

Jiang, 1991, Membrane properties and synaptic responses of rat striatal neurones in vitro, J. Physiol., 443, 533, 10.1113/jphysiol.1991.sp018850

Jones, M.W., McClean, M., Parsons, C.G., Headley, P.M., 1999. The in vivo relevance of the varied channel-blocking properties of uncompetitive NMDA receptor antagonists. Neuropharmacology, (submitted).

Karcz-Kubicha, 1997, Anxiolytic activity of glycine-B antagonists and partial agonists—no relation to intrinsic activity in the patch clamp, Neuropharmacology, 36, 1355, 10.1016/S0028-3908(97)00130-5

Karobath, 1974, Amantadine and D-145, an amantadine derivative, do not effect dopamine sensitive adenylate cyclase from the caudate-putamen of the rat brain, Eur. J. Pharmacol., 28, 376, 10.1016/0014-2999(74)90292-1

Keilhoff, 1992, Memantine prevents quinolinic acid-induced hippocampal damage, Eur. J. Pharmacol., 219, 451, 10.1016/0014-2999(92)90487-O

Klee, 1982, The effect of memantine on membrane properties and postsynaptic potentials in neurones of Aplysia californica, Arzneim. Forsch. Drug Res., 32, 1259

Kleinrok, 1995, Excitatory amino acid antagonists and the anticonvulsive activity of conventional antiepileptic drugs, Pol. J. Pharmacology, 47, 247

Kleiser, 1995, Combined therapy with flunarizine and memantine of experimental intracerebral hematomas in rats, Neurol. Psychiatry, 3, 219

Klockgether, 1993, Toward an understanding of the role of glutamate in experimental parkinsonism-agonist-sensitive sites in the basal ganglia, Ann. Neurol., 34, 585, 10.1002/ana.410340413

Knecht, 1996, Decreased glutamate transporter (GLT-1) gene expression in brain in acute liver failure, Hepatology, 24, 486

Knipper, 1997, Transient expression of NMDA receptors during rearrangement of AMPA-receptor-expressing fibers in the developing inner ear, Cell Tissue Res., 287, 23, 10.1007/s004410050729

Koek, 1988, MK-801, a proposed non-competitive antagonist of excitatory amino acid neurotransmission, produces phencyclidine-like behavioural effects in pigeons, rats and rhesus monkeys, J. Pharmacol. Exp. Ther., 245, 969

Koplovitz, 1997, Memantine effects on soman-induced seizures and seizure-related brain damage, Toxicol. Method, 7, 227, 10.1080/105172397243178

Kornhuber, 1991, Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study, Eur. J. Pharmacol. Molec. Pharmacol., 206, 297, 10.1016/0922-4106(91)90113-V

Kornhuber, 1989, Memantine displaces 3H-MK-801 at therapeutic concentrations in postmortem human frontal cortex, Eur. J. Pharmacol., 166, 589, 10.1016/0014-2999(89)90384-1

Kornhuber, 1995, Cerebrospinal fluid and serum concentrations of the N-methyl-d-aspartate (NMDA) receptor antagonist memantine in man, Neurosci. Lett., 195, 137, 10.1016/0304-3940(95)11785-U

Kornhuber, 1993, Affinity of 1-aminoadamantanes for the sigma binding site in post-mortem human frontal cortex, Neurosci. Lett., 163, 129, 10.1016/0304-3940(93)90362-O

Kornhuber, 1997, Psychotogenicity and N-methyl-d-aspartate receptor antagonism: implications for neuroprotective pharmacotherapy, Biol. Psychiatry, 41, 135, 10.1016/S0006-3223(96)00047-9

Kornhuber, 1994, Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties, J. Neural Transm. Gen. Sect., 43, 91

Koros, E., Kostowski, W., Danysz, W., Bienkowski, P. 1999. Ethanol discrimination in the rat: lack of modulation by restraint stress and memantine. Naunyn-Schmied. Arch. Pharmacol. 359, 117–122.

Krieglstein, 1997, Neuroprotection by memantine as increased by hypothermia and nimodipine, Eur. J. Pharm. Sci., 5, 71, 10.1016/S0928-0987(96)00257-6

Krieglstein, 1996, Apparent independent action of nimodipine and glutamate antagonists to protect cultured neurones against glutamate-induced damage, Neuropharmacology, 35, 1737, 10.1016/S0028-3908(96)00104-9

Lagreze, 1998, Memantine is neuroprotective in a rat model of pressure-induced retinal ischemia, Invest. Ophthalmol. Vis. Sci., 39, 1063

Lampe, 1991, Modulation of glycine-activated membrane current by adamantane derivatives, Neuroreport, 2, 373, 10.1097/00001756-199107000-00004

Laschka, 1976, Activity of the nigro-striatal dopaminergic system during precipitated morphine withdrawal investigated in rats with acute unilateral inactivation of the striatum, Naunyn-Schmied. Arch. Pharmacol., 296, 15, 10.1007/BF00498835

Laurie, 1994, Ligand affinities at recombinant N-methyl-d-aspartate receptors depend on subunit composition, Eur. J. Pharmacol. Molec. Pharmacol., 268, 335, 10.1016/0922-4106(94)90058-2

Lehmann, 1996, Effects of N-methyl-d-aspartate receptor antagonists on cisplatin-induced emesis in the ferret, Neuropharmacology, 35, 475, 10.1016/0028-3908(96)00008-1

Leppik, 1988, MK-801 for epilepsy: a pilot study, Neurology, 38, 405

Lipton, 1992, Memantine prevents HIV coat protein-induced neuronal injury in vitro, Neurology, 42, 1403, 10.1212/WNL.42.7.1403

Lipton, 1994, AIDS-related dementia and calcium homeostasis, Ann. NY Acad. Sci., 747, 205, 10.1111/j.1749-6632.1994.tb44411.x

Lipton, 1997, Neuropathogenesis of acquired immunodeficiency syndrome dementia, Curr. Opin. Neurol., 10, 247, 10.1097/00019052-199706000-00014

Ljungberg, 1986, Locomotion and stereotyped behaviours induced by 1-amino-3,5-dimethyladamantane (D 145) and apomorphine in the rat: a comparison, J. Pharm. Pharmacol., 38, 520, 10.1111/j.2042-7158.1986.tb04627.x

Löscher, 1982, High doses of memantine (1-amino-3,5-dimethyladamantane) induce seizures in kindled but not in non-kindled rats, Naunyn-Schmied. Arch. Pharmacol., 341, 476

Löscher, 1994, Over-additive anticonvulsant effect of memantine and NBQX in kindled rats, Eur. J. Pharmacol., 259, R3, 10.1016/0014-2999(94)90514-2

Lupp, 1992, Inhibitory effects of the antiparkinsonian drugs memantine and amantadine on N-methyl-d-aspartate-evoked acetylcholine release in the rabbit caudate nucleus in vitro, J. Pharmacol. Exp. Ther., 263, 717

Maj, 1975, The influence of dopaminergic agents on the serotonergic neurons, Pol. J. Pharmacol. Pharm., 27, 45

Maj, 1977, Dopamine agonists and interaction with other neurotransmitter systems, Naunyn-Schmied. Arch. Pharmacol., 297, 53, 10.1007/BF00587777

Maj, 1982, Effect of memantine on central neurotransmitter systems. Review of the results, Arzneim. Forsch. Drug Res., 32, 1256

Maj, 1977, Dopaminergic stimulation enhances the utilization of noradrenaline in the central nervous system, J. Pharm. Pharmacol., 29, 569, 10.1111/j.2042-7158.1977.tb11402.x

Maj, 1974, Pharmacological effects of 1,3-dimethyl-5-adamantane, a new adamantane derivative, Eur. J. Pharmacol., 269, 9, 10.1016/0014-2999(74)90067-3

Malec, 1981, Central action of narcotic analgesics VIII. The effect of dopaminergic stimulants on the action of analgesics in rats, Pol. J. Pharmacol. Pharm., 33, 273

Masuo, 1986, Effects of memantine on the frog neuromuscular junction, Eur. J. Pharmacol., 130, 187, 10.1016/0014-2999(86)90267-0

Matsubayashi, 1997, Amantadine inhibits nicotinic acetylcholine receptor function in hippocampal neurons, J. Pharmacol. Exp. Ther., 281, 834

McClean, 1996, In vivo significance of the different voltage dependence of uncompetitive and glycineB NMDA antagonists, Soc. Neurosci. Abs., 22, 1531

McLean, 1987, In vitro electrophysiological evidence predicting anticonvulsant efficacy of memantine and flunarizine, Pol. J. Pharmacol. Pharm., 39, 513

McLean, 1992, Prophylactic and therapeutic efficacy of memantine against seizures produced by soman in the rat, Toxicol. Appl. Pharmacol., 112, 95, 10.1016/0041-008X(92)90284-Y

Mealing, 1997, Antagonism of N-methyl-d-aspartate-evoked currents in cortical cultures by ARL 15896AR, J. Pharmacol. Exp. Ther., 281, 376

Meldrum, 1992, Excitatory amino acid receptors and disease, Curr. Opin. Neurol. Neurosurg., 5, 508

Meldrum, 1986, Anticonvulsant action of 1,3-dimethyl-5-aminoadamantane. Pharmacological studies in rodents and baboon, Papio Papio, Naunyn-Schmied. Arch. Pharmacol., 332, 93, 10.1007/BF00633204

Menon, 1978, Pharmacological evidence for the involvement of GABA-ergic system in the locomotor stimulation produced in mice by 1,3-dimethyl-5-aminoadamantane (d-145), Neuropharmacology, 17, 1049, 10.1016/0028-3908(78)90033-3

Menon, 1979, GABA-ergic drugs block the locomotor stimulant effects of 1,3-dimethyl-5-aminoadamantane (d-145), Neuropharmacology, 18, 223, 10.1016/0028-3908(79)90066-2

Menon, 1984, Evidence for presynaptic antagonism by amantadine of indirectly acting central stimulants, Psychopharmacology, 82, 89, 10.1007/BF00426387

Messiha, 1988, Effect of amantadine on chlorpromazine and reserpine-induced behavioral depression in the mouse, Neurosci. Biobehav. Rev., 12, 219, 10.1016/S0149-7634(88)80046-0

Michalak, 1997, Selective loss of binding sites for the glutamate receptor ligands [3H]kainate and (S)-[3H]5-fluorowillardiine in the brains of rats with acute liver failure, Hepatology, 25, 631, 10.1002/hep.510250323

Michalak, 1996, Neuroactive amino acids and glutamate (NMDA) receptors in frontal cortex of rats with experimental acute liver failure, Hepatology, 24, 908, 10.1002/hep.510240425

Michalak, 1997, Hepatic encephalopathy in acute liver failure: role of the glutamate system

Miguel-Hidalgo, 1998, Protection by memantine against Aβ(1-40.)-induced neurodegeneration in the CA1 subfield, Neurobiol. Aging, 19, 542

Millan, 1994, Chemically-diverse ligands at the glycineB site coupled to N-methyl-d-aspartate (NMDA) receptors selectively block the late phase of formalin-induced pain in mice, Neurosci. Lett., 178, 139, 10.1016/0304-3940(94)90309-3

Miltner, 1982, Use of symptomatic therapy with memantine in cerebral coma. II. Development of stretch syergisms in coma with brain stem symptoms, Arzneim. Forsch. Drug Res., 32, 1271

Miltner, 1982, Use of symptomatic therapy with memantine in cerebral coma. I. Correlation of coma stages and EEG spectral patterns, Arzneim. Forsch. Drug Res., 32, 1268

Mistry, 1995, Modulation of NMDA effects on agonist-stimulated phospho-inositide turnover by memantine in neonatal rat cerebral cortex, Br. J. Pharmacol., 114, 797, 10.1111/j.1476-5381.1995.tb13275.x

Misztal, 1995, Comparison of glutamate antagonists in continuous multiple-trial and single-trial dark avoidance, Behav. Pharmacol., 6, 550, 10.1097/00008877-199508000-00015

Misztal, 1996, Learning deficits induced by chronic intraventricular infusion of quinolinic acid-protection by MK-801 and memantine, Eur. J. Pharmacol., 296, 1, 10.1016/0014-2999(95)00682-6

Mitani, 1992, Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil-brain microdialysis study, Neuroscience, 48, 307, 10.1016/0306-4522(92)90492-K

Mizuno, 1994, Practical guidelines for the drug treatment of Parkinson’s disease, CNS Drugs, 1, 410, 10.2165/00023210-199401060-00003

Mogilnicka, 1977, The influence of antiserotonergic agents on the action of dopaminergic drugs, Pol. J. Pharmacol. Pharm., 29, 31

Monaghan, 1997, NR1 and NR2 subunit contributions to N-methyl-d-aspartate receptor channel blocker pharmacology, J. Pharmacol. Exp. Ther., 280, 614

Monassier, 1996, MK-801 and memantine inhibit a centrally induced increase in myocardial oxygen demand in rabbits, Eur. J. Pharmacol., 305, 109, 10.1016/0014-2999(96)00170-7

Mondadori, 1989, NMDA receptor antagonists can enhance or impair learning performance in animals, Exp. Brain Res., 75, 449, 10.1007/BF00249896

Moniuszko-Jakoniuk, 1977, Interaction of bradykinin with dopaminergic receptors in the CNS, Pol. J. Pharmacol. Pharm., 29, 301

Monyer, 1994, Developmental and regional expression in the rat brain and functional properties of four NMDA receptors, Neuron, 12, 529, 10.1016/0896-6273(94)90210-0

Monyer, 1992, Heteromeric NMDA receptors-molecular and functional distinction of subtypes, Science, 256, 1217, 10.1126/science.256.5060.1217

Moryl, 1993, Potential antidepressive properties of amantadine, memantine and bifemelane, Pharmacol. Toxicol., 72, 394, 10.1111/j.1600-0773.1993.tb01351.x

Mühlberg, 1973, The depression of monosynaptically excited alpha-motoneurons during vibration reflex by dimethylaminoadamantan (DMAA), Naunyn-Schmied. Arch. Pharmacol., 280, 113, 10.1007/BF00505361

Muir, 1995, Clinical experience with excitatory amino acid antagonist drugs, Stroke, 26, 503, 10.1161/01.STR.26.3.503

Müller, 1995, Noncompetitive NMDA receptor antagonists with fast open-channel blocking kinetics and strong voltage-dependency as potential therapeutic agents for Alzheimer’s dementia, Pharmacopsychiatry, 28, 113, 10.1055/s-2007-979603

Müller, 1996, Neurotoxicity in rat cortical cells caused by N-methyl-d-aspartate (NMDA) and gp120 of HIV-1: induction and pharmacological intervention, Prog. Mol. Subcell. Biol, 16, 44, 10.1007/978-3-642-79850-4_3

Müller, 1997, Interaction of prion protein mRNA with CBP35 and other cellular proteins—possible implications for prion replication and age-dependent changes, Arch. Gerontol. Geriatr., 25, 41, 10.1016/S0167-4943(96)00770-4

Müller, 1992, Gp120 of HIV-1 induces apoptosis in rat cortical cell cultures-prevention by memantine, Eur. J. Pharmacol. Molec. Pharmacol., 226, 209, 10.1016/0922-4106(92)90063-2

Müller, 1993, Cytoprotective effect of NMDA receptor antagonists on prion protein (Prion (Sc))-induced toxicity in rat cortical cell cultures, Eur. J. Pharmacol. Mol. Pharmacol., 246, 261, 10.1016/0922-4106(93)90040-G

Mundinger, 1985, Treatment of severe spastic and extrapyramidal syndromes with Memantine, in combination or following stereotactic surgery, Nervenarzt, 56, 106

Nankai, 1995, Striatal NMDA receptor subtypes: The pharmacology of N-methyl-d-aspartate-evoked dopamine, gamma-aminobutyric acid, acetylcholine and spermidine release, Eur. J. Pharmacol., 286, 61, 10.1016/0014-2999(95)00429-O

Nankai, 1995, NMDA receptor subtype selectivity: Eliprodil, polyamine spider toxins, dextromethorphan, and desipramine selectively block NMDA-evoked striatal acetylcholine but not spermidine release, J. Neurochem., 64, 2043, 10.1046/j.1471-4159.1995.64052043.x

Nankai, 1996, Evidence for native NMDA receptor subtype pharmacology as revealed by differential effects on the NMDA-evoked release of striatal neuromodulators: eliprodil, ifenprodil and other native NMDA receptor subtype selective compounds, Neurochem. Int., 29, 529, 10.1016/0197-0186(96)00010-1

Nankai, 1998, The pharmacology of native N-methyl-d-aspartate receptor subtypes: different receptors control the release of different striatal and spinal transmitters, Prog. Neuro. Psych. Biol Psych., 22, 35, 10.1016/S0278-5846(97)00180-2

Netzer, 1990, Memantine reduces repetitive action potential firing in spinal cord nerve cell cultures, Eur. J. Pharmacol., 186, 149, 10.1016/0014-2999(90)90428-9

Netzer, 1986, Convulsant induced hyperactivity in cultured spinal cord neurons: a model for antiepileptic drug action, Naunyn-Schmied. Arch. Pharmacol., 332, 93

Neugebauer, 1993, The clinically available NMDA receptor antagonist memantine is antinociceptive on rat spinal neurones, Neuroreport, 4, 1259, 10.1097/00001756-199309000-00012

Nicholson, 1998, Evaluation of the reinforcing and discriminative stimulus properties of the low-affinity N-methyl-d-aspartate channel blocker memantine, Behav. Pharmacol., 9, 231

Niedzielski, 1997, Molecular analysis of excitatory amino acid receptor expression in the cochlea, Audiol. Neuro. Otol., 2, 79, 10.1159/000259232

Noth, 1991, Trends in the pathophysiology and pharmacotherapy of spasticity, J. Neurol., 238, 131, 10.1007/BF00319679

Nowak, 1984, Magnesium gates glutamate-activated channels in mouse central neurons, Nature, 307, 462, 10.1038/307462a0

Oestreicher, 1998, Memantine suppresses the glutamatergic neurotransmission of mammalian inner hair cells, ORL J. Otorhinolaryngol. Relat. Spec., 60, 18, 10.1159/000027556

Olivar, 1997, Differential effects of NMDA receptor antagonists on nociceptive reflexes of somatic and visceral origin, Soc. Neurosci. Abs., 23, 2

Oppong, 1995, Synaptosomal glutamate transport in thioacetamide-induced hepatic encephalopathy in the rat, Hepatology, 22, 553

Osborne, 1982, The effect of memantine on various neurobiological processes, Arzneim. Forsch. Drug Res., 32, 1246

Osborne, 1992, Memantine stimulates inositol phosphates production in neurones and nullifies N-methyl-d-aspartate-induced destruction of retinal neurones, Neurochem. Int., 21, 329, 10.1016/0197-0186(92)90183-R

Ossowska, 1997, The effect of NMDA antagonists on footshock-induced fighting behavior in chronically stressed rats, J. Physiol. Pharmacol., 48, 127

Palmer, 1990, Is the neuronal basis of Alzheimer’s disease cholinergic or glutamatergic?, FASEB J., 4, 2745, 10.1096/fasebj.4.10.2165009

Pantev, 1993, Clinical and behavioural evaluation in long-term care patients with mild to moderate dementia under memantine treatment, Zeitschrift für Gerontopsychologie und Psychiatrie, 6, 103

Parsons, 1999, Amino-alkyl-cyclohexanes are novel uncompetitive NMDA receptor antagonists with strong voltage-dependency and fast blocking kinetics: in vitro and in vivo characterization, Neuropharmacology, 38, 85, 10.1016/S0028-3908(98)00161-0

Parsons, C.G., Danysz, W., Quack, G., 1998c. Glutamate in CNS Disorders as a target for drug development—an update. Drug News Perspect. 11, 523–569.

Parsons, 1993, Patch clamp studies on the kinetics and selectivity of N-methyl-d-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan), Neuropharmacology, 32, 1337, 10.1016/0028-3908(93)90029-3

Parsons, 1998, The amino-alkyl-cyclohexane MRZ 2/579 is an uncompetitive NMDA Receptor antagonist with fast blocking kinetics and strong voltage-dependency, Soc. Neurosci. Abs., 24, 7

Parsons, 1998, Budipine is a low affinity, N-methyl-d-aspartate receptor antagonist: patch clamp studies in cultured striatal, hippocampal, cortical and superior colliculus neurone, Neuropharmacology, 37, 719, 10.1016/S0028-3908(98)00059-8

Parsons, 1994, Comparative studies on NMDA receptor antagonism by amantadine (1-aminoadamantane) and memantine (1-amino,3,5-dimethyladmantane), Soc. Neurosci. Abs., 20, 7

Parsons, 1996, Comparative patch clamp studies with freshly dissociated rat hippocampal and striatal neurones on the NMDA receptor antagonistic effects of amantadine and memantine, Eur. J. Neurosci., 8, 446, 10.1111/j.1460-9568.1996.tb01228.x

Parsons, 1991, Disturbed glutamatergic transmission in dementia: improvement by akatinol memantine, Behav. Pharmacol., 388, 39

Parsons, 1995, Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo, Neuropharmacology, 34, 1239, 10.1016/0028-3908(95)00092-K

Parsons, 1989, Spinal antinociceptive actions and naloxone reversibility of intravenous mu- and kappa-opioids in spinalized rats: potency mismatch with values reported for spinal administration, Br. J. Pharmacol., 98, 533, 10.1111/j.1476-5381.1989.tb12627.x

Pellegrini, 1993, Delayed administration of memantine prevents N-methyl-d-aspartate receptor mediated neurotoxicity, Ann. Neurol., 33, 403, 10.1002/ana.410330414

Pittaluga, 1994, HIV-1 envelope protein gp120 potentiates NMDA-evoked noradrenaline release by a direct action at rat hippocampal and cortical noradrenergic nerve endings, Eur. J. Neurosci., 6, 1743, 10.1111/j.1460-9568.1994.tb00566.x

Pittaluga, 1996, Human brain N-methyl-d-aspartate receptors regulating noradrenaline release are positively modulated by HIV-1 coat protein gp120, AIDS, 10, 463, 10.1097/00002030-199605000-00003

Popik, 1997, Inhibition of reinforcing effects of morphine and motivational aspects of naloxone-precipitated opioids withdrawal by N-methyl-d-aspartate receptor antagonist, memantine, J. Pharmacol. Exp. Ther., 280, 854

Popik, 1996, The NMDA antagonist memantine blocks the expression and maintenance of morphine dependence, Pharmacol. Biochem. Behav., 53, 791, 10.1016/0091-3057(95)02163-9

Porter, 1995, Regional variations in the pharmacology of NMDA receptor channel blockers: implications for therapeutic potential, J. Neurochem., 64, 614, 10.1046/j.1471-4159.1995.64020614.x

Prado de Carvalho, 1993, NMDA receptors expressed in oocytes: effects of ligands related to HIV infection, Soc. Neurosci. Abs., 1, 16

Procter, 1989, Loss of glycine-dependent radioligand binding to the N-methyl-d-aspartate-phencyclidine receptor complex in patients with Alzheimer’s disease, Neurosci. Lett., 101, 62, 10.1016/0304-3940(89)90441-2

Procter, 1991, Characterisation of the glycine modulatory site of the N-methyl-d-aspartate receptor ionophore complex in human brain, J. Neurochem., 56, 299, 10.1111/j.1471-4159.1991.tb02596.x

Procter, 1989, Reduced glycine stimulation of MK-801 binding in Alzheimer’s disease, J. Neurochem., 53, 698, 10.1111/j.1471-4159.1989.tb11760.x

Puel, 1995, Chemical synaptic transmission in the cochlea, Prog. Neurobiol., 47, 449, 10.1016/0301-0082(95)00028-3

Puel, 1997, Synaptic repair mechanisms responsible for functional recovery in various cochlear pathologies, Acta Oto. Laryngol., 117, 214, 10.3109/00016489709117773

Quack, 1995, Microdialysis studies with amantadine and memantine on pharmacokinetics and effects on dopamine turnover (Gen. Sect.), J. Neural Transm., 46, 97

Raber, 1996, Central nervous system expression of HIV-1 gp120 activates the hypothalamic-pituitary-adrenal axis: evidence for involvement of NMDA receptors and nitric oxide synthase, Virology, 226, 362, 10.1006/viro.1996.0664

Rabey, 1992, Efficacy of memantine, and NMDA receptor antagonist, in the treatment of Parkinson’s disease (P.D. Section), J. Neural Transm., 4, 277, 10.1007/BF02260076

Raboisson, 1997, MK-801 neurotoxicity in the guinea pig cerebral cortex: Susceptibility and regional differences compared with the rat, J. Neurosci. Res., 49, 364, 10.1002/(SICI)1097-4547(19970801)49:3<364::AID-JNR11>3.0.CO;2-#

Randrup, 1976, Pharmacology of monoaminergic mechanisms, Pol. J. Pharmacol. Pharm., 28, 551

Reiser, 1988, Memantine (1-amino-3,5-dimethyladamantane) blocks the serotonin-induced depolarization response in a neuronal cell line, Brain Res., 443, 338, 10.1016/0006-8993(88)91630-7

Reiser, 1989, Memantine inhibits serotonin-induced rise of cytosolic Ca2+ activity and of cyclic GMP level in a neuronal cell line, Eur. J. Pharmacol. Molec. Pharmacol., 172, 199, 10.1016/0922-4106(89)90011-4

Richter, 1991, Antidystonic effects of the NMDA receptor antagonists memantine, MK-801 and CGP 37849 in a mutant hamster model of paroxysmal Dystonia, Neurosci. Lett., 133, 57, 10.1016/0304-3940(91)90056-Y

Riederer, 1991, Pharmacotoxic psychosis after memantine in Parkinson’s disease [22], Lancet, 338, 1022, 10.1016/0140-6736(91)91888-2

Rodriguez Paz, 1995, Block of the N-methyl-d-aspartate receptor by phencyclidine-like drugs is influenced by alternative splicing, Neurosci. Lett., 190, 147, 10.1016/0304-3940(95)11524-Z

Rogawski, 1993, Therapeutic potential of excitatory amino acid antagonists -channel blockers and 2,3–benzodiazepines, Trends Pharmacol. Sci., 14, 325, 10.1016/0165-6147(93)90005-5

Rogawski, 1991, Anticonvulsant activity of the low-affinity uncompetitive N-Methyl-d-Aspartate antagonist (+/−)-5-aminocarbonyl-10,11-dihydro-5H-dibenzo<a,d>cyclohepten-5, 10-imine (ADCI)-comparison with the structural analogs dizocilpine (MK-801) and carbamazepine, J. Pharmacol. Exp. Ther., 259, 30

Rohrbacher, 1994, Suppression by memantine and amantadine of synaptic excitation intrastriatally evoked in rat neostriatal slices, Neurosci. Lett., 182, 95, 10.1016/0304-3940(94)90215-1

Ruppersberg, 1994, The mechanism of magnesium block of NMDA receptors, Semin. Neurosci., 6, 87, 10.1006/smns.1994.1012

Rytik, 1991, Susceptibility of primary human glial fibrillary acidic protein-positive brain cells to human immunodeficiency virus infection in vitro: anti-HIV activity of memantine, AIDS Res. Hum. Retroviruses, 7, 89, 10.1089/aid.1991.7.89

Sakurada, 1993, Alteration of Ca2+ permeability and sensitivity to Mg2+ and channel blockers by a single amino acid substitution in the N-methyl-d-aspartate receptor, J. Biol. Chem., 268, 410, 10.1016/S0021-9258(18)54166-1

Samnick, 1997, Synthesis and preliminary in vitro evaluation of a new memantine derivative 1-amino-3-[18F]fluoromethyl-5-methyl-adamantane: a potential ligand for mapping the N-methyl-d-aspartate receptor complex, J. Label. Comp. Radiopharm., 39, 241, 10.1002/(SICI)1099-1344(199703)39:3<241::AID-JLCR966>3.0.CO;2-V

Samnick, 1998, Electrophysiological study, biodistribution in mice, and preliminary PET evaluation in a rhesus monkey of 1-amino-3-[18F]fluoromethyl-5-methyl-adamantane (18F-MEM): a potential radioligand for mapping the NMDA-receptor complex, Nucl. Med. Biol., 25, 323, 10.1016/S0969-8051(98)00003-1

Sanger, 1992, NMDA antagonists disrupt timing behaviour in rats, Behav. Pharmacol., 3, 593, 10.1097/00008877-199212000-00006

Sanger, 1992, Memantine has phencyclidine-like but not cocaine-like discriminative stimulus effects in rats, Behav. Pharmacol., 3, 265, 10.1097/00008877-199206000-00011

Scatton, 1994, Pharmacology of excitatory amino acid receptors-novel therapeutic approaches in neurodegenerative disorders, 157

Schmidt, 1992, Behavioural pharmacology of glutamate in the basal ganglia (P-D-Section), J. Neural Transm., 38, 65

Schmidt, 1997, Behavioural pharmacology of glutamate receptors in the basal ganglia, Neurosci. Biobehav. Rev., 21, 381, 10.1016/S0149-7634(96)00044-9

Schmidt, 1991, Anticataleptic potencies of glutamate-antagonists, Amino Acids, 1, 115, 10.1007/BF00806920

Schneider, 1984, Effects of oral memantine on symptoms of Parkinson’s disease, Dtsch. Med. Wochenschr., 109, 987, 10.1055/s-2008-1069311

Schügens, 1997, The NMDA antagonist memantine impairs classical eyeblink conditioning in humans, Neurosci. Lett., 224, 57, 10.1016/S0304-3940(97)13452-8

Schulz, 1996, The use of diurnal vigilance changes in the EEG to verify vigilance-enhancing effects of memantine in a clinical pharmacological study, Neuropsychobiology, 33, 32, 10.1159/000119246

Schulz, 1996, Neuroprotective strategies for treatment of lesions produced by mitochondrial toxins: implications for neurodegenerative diseases, Neuroscience, 71, 1043, 10.1016/0306-4522(95)00527-7

Schwarz, 1992, N-methyl-d-aspartate (NMDA)-mediated muscle relaxant action of memantine in rats, Neurosci. Lett., 143, 105, 10.1016/0304-3940(92)90243-Z

Schwarz, 1995, N-Methyl-d-aspartate and alpha–adrenergic mechanisms are involved in the depressant action of flupirtine on spinal reflexes in rats, Eur. J. Pharmacol., 276, 247, 10.1016/0014-2999(95)00043-K

Seif El Nasr, 1990, Neuroprotective effect of memantine demonstrated in vivo and in vitro, Eur. J. Pharmacol., 185, 19, 10.1016/0014-2999(90)90206-L

Semenova, S.G., Kuzmin, A.V., Danysz, W., Bespalov, A.Y. Low-affinity NMDA receptor channel blockers inhibit initiation of intravenous morphine self-administration in naive mice. Eur. J. Pharmacol. (submitted).

Shih, 1996, Evaluation of anticonvulsant drugs for soman induced seizure activity, J. Am. Coll. Toxicol., 15, S43, 10.3109/10915819609048337

Skuza, 1994, Memantine, amantadine, and l-deprenyl potentiate the action of l-DOPA in monoamine-depleted rats, J. Neural Transm. Gen. Sect., 98, 57, 10.1007/BF01277594

Smialowska, 1976, Histofluorescence studies on the effect of 1,3-dimethyl-5-adamantanamine (d-145) on serotonergic neurons in midbrain Raphe nuclei, Pol. J. Pharmacol. Pharm., 28, 233

Sobolevsky, 1998, Two blocking sites of amino-adamantane derivatives in open N- methyl-d-aspartate channels, Biophys. J., 74, 1305, 10.1016/S0006-3495(98)77844-0

Sobolevsky, 1998, Interaction of memantine and amantadine with agonist-unbound NMDA-receptor channels in acutely isolated rat hippocampal neurons, J. Physiol., 512, 47, 10.1111/j.1469-7793.1998.047bf.x

Sontag, 1973, Decrease of muscle rigidity by dimethylaminoadamantan (DMMA) in intercollicularly decerebrated cats, Arzneim. Forsch. Drug Res., 23, 1737

Sontag, 1974, The reduction of excitability of the γ-loop by 1,3-dimethyl-5-aminoadamantane (DMAA), Naunyn-Schmied. Arch. Pharmacol., 286, 315, 10.1007/BF00498313

Sontag, 1982, The effect of memantine on spinal a-motoneurones and on content of dopamine, noradrenaline and serotonin of striatum and lumbar spinal cord, Arzneim. Forsch. Drug Res., 32, 1236

Spanagel, 1994, Memantine-induced dopamine release in the prefrontal cortex and striatum of the rat-a pharmacokinetic microdialysis study, Eur. J. Pharmacol., 262, 21, 10.1016/0014-2999(94)90023-X

Spanagel, 1997, Anti-craving compounds for ethanol: new pharmacological tools to study addictive processes, Trends Pharmacol. Sci., 18, 54, 10.1016/S0165-6147(97)89800-8

Spielmanns, 1998, Subtype selectivity of memantine, amantadine and MRZ 2/579 on NMDA receptors expressed in Xenopus oocytes, Soc. Neurosci. Abs., 24, 6

Spüler, 1986, Radioencephalographic monitoring of dopaminergic drug effects in the rat (tele-stereo-EEG), Naunyn-Schmied. Arch. Pharmacol., 332, 361

Starck, 1997, Drug therapy for acquired pendular nystagmus in multiple sclerosis, J. Neurol., 244, 9, 10.1007/PL00007728

Starr, 1995, Antiparkinsonian actions of glutamate antagonists-alone and with l-DOPA: a review of evidence and suggestions for possible mechanisms (P-D-Section), J. Neural Transm., 10, 141, 10.1007/BF02251229

Starr, 1995, Locomotor effects of amantadine in the mouse are not those of a typical glutamate antagonist (P-D-Section), J. Neural Transm., 9, 31, 10.1007/BF02252961

Stieg, 1993, Post-stroke neuroprotection by memantine minimally affects behavior and does not block LTP, Soc. Neurosci. Abs., 19, 9

Stoof, 1992, The anti-Parkinsonian drug amantadine inhibits the N-methyl-d-aspartic acid-evoked release of acetylcholine from rat neostriatum in a non-competitive way, Eur. J. Pharmacol., 213, 439, 10.1016/0014-2999(92)90634-G

Subramaniam, 1994, Hydrophobic interactions of N-alkyl diamines with the N-methyl-d-aspartate receptor-voltage-dependent and-independent blocking sites, Mol. Pharmacol., 45, 117

Sveinbjornsdottir, 1993, The excitatory amino acid antagonist d-CPP-ene (SDZ EAA-494) in patients with epilepsy, Epilepsy Res., 16, 165, 10.1016/0920-1211(93)90031-2

Svensson, 1992, Differential locomotor interactions between dopamine-D1/D2 receptor agonists and the NMDA antagonist dizocilpine in monoamine-depleted mice (Gen. Sect.), J. Neural Transm., 90, 199, 10.1007/BF01250961

Svensson, 1973, Dopamine release and direct dopamine receptor activation in the central nervous system by d-145, an amantadine derivative, Eur. J. Pharmacol., 23, 232, 10.1016/0014-2999(73)90088-5

Taniguchi, 1997, Antinociceptive activity of CP-101,606, an NMDA receptor NR2B subunit antagonist, Br. J. Pharmacol., 122, 809, 10.1038/sj.bjp.0701445

Toggas, 1996, Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine, Brain Res., 706, 303, 10.1016/0006-8993(95)01197-8

Tomitaka, 1997, Regionally different effects of scopolamine on NMDA antagonist-induced heat shock protein HSP70, Brain Res., 763, 255, 10.1016/S0006-8993(97)00497-6

Tomitaka, 1996, Memantine induces heat shock protein HSP70 in the posterior cingulate cortex, retrosplenial cortex and dentate gyrus of rat brain, Brain Res., 740, 1, 10.1016/S0006-8993(96)00842-6

Toru, 1994, Minireview: excitatory amino acids: implications for psychiatric disorders research, Life Sci., 55, 1683, 10.1016/0024-3205(94)00337-8

Tsai, 1989, Effects of memantine on the twitch tension of mouse diaphragm, Eur. J. Pharmacol., 160, 133, 10.1016/0014-2999(89)90662-6

Tzschentke, 1998, Effects of memantine on brain-stimulation reward, Eur. J. Neurosci., 10, 311

Uitti, 1996, Amantadine treatment is an independent predictor of improved survival in Parkinson’s disease, Neurology, 46, 1551, 10.1212/WNL.46.6.1551

Ulas, 1994, Selective increase of NMDA-sensitive glutamate binding in the striatum of Parkinson’s disease, Alzheimer’s disease, and mixed Parkinson’s disease/Alzheimer’s disease patients: an autoradiographic study, J. Neurosci., 14, 6317, 10.1523/JNEUROSCI.14-11-06317.1994

Urbanska, 1992, Antiparkinsonian drugs memantine and trihexyphenidyl potentiate the anticonvulsant activity of valproate against maximal electroshock-induced seizures, Neuropharmacology, 31, 1021, 10.1016/0028-3908(92)90103-V

Ushijima, 1993, HIV-1 gp120 and NMDA induce protein kinase-C translocation differentially in rat primary neuronal cultures, J. Acq. Immun. Defic. Syndrome, 6, 339

Ushijima, 1995, Exposure to gp120 of HIV-1 induces an increased release of arachidonic acid in rat primary neuronal cell culture followed by NMDA receptor-mediated neurotoxicity, Eur. J. Neurosci., 7, 1353, 10.1111/j.1460-9568.1995.tb01126.x

Vale, 1971, Amantadine in depression, Lancet, 11, 437, 10.1016/S0140-6736(71)90153-X

Verspohl, 1988, Interaction of memantine with cholecystikinin receptors in mouse brain, J. Pharm. Pharmacol., 40, 111, 10.1111/j.2042-7158.1988.tb05192.x

Vogels, 1997, Memantine, a non-competitive NMDA-receptor antagonist improves hyperammonemia-induced encephalopathy and acute hepatic encephalopathy in rats, Hepatology, 25, 820, 10.1002/hep.510250406

Von Euler, 1997, No protective effect of the NMDA antagonist memantine in experimental spinal cord injuries, J. Neurotrauma, 14, 53, 10.1089/neu.1997.14.53

Vorwerk, 1996, Chronic low-dose glutamate is toxic to retinal ganglion cells -toxicity blocked by memantine, Invest. Ophthalmol. Visual Sci., 37, 1618

Wallstrom, 1996, Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune encephalomyelitis, J. Neurol. Sci., 137, 89, 10.1016/0022-510X(95)00339-4

Wand, 1977, Effects of 1,3 dimethyl 5 aminoadamantane hydrochloride (DMAA) on the stretch induced reflex tension of flexor muscles and the excitability of the g loop in decerebrate and spinal cats, Arzneim. Forsch. Drug Res., 27, 1477

Wang, 1995, Modulation by magnesium of the affinity of NMDA receptors for glycine in murine hippocampal neurones, J. Physiol., 486, 83, 10.1113/jphysiol.1995.sp020792

Wang, 1994, Magnesium and ketamine increase the affinity of NMDA receptors for glycine, Soc. Neurosci. Abs., 20, 734

Wang, 1995, Memantine, a clinically tolerated NMDA antagonist, decreases infarct size in spontaneously hypertensive rats when administered 2 h post ischemic-reperfusion cerebral injury, Neurology, 45, 526P

Weihmuller, 1992, Elevated NMDA receptors in Parkinsonian striatum, Neuroreport, 3, 977, 10.1097/00001756-199211000-00007

Weller, 1993, NMDA receptor-mediated glutamate toxicity of cultured cerebellar, cortical and mesencephalic neurons: neuroprotective properties of amantadine and memantine, Brain Res., 613, 143, 10.1016/0006-8993(93)90464-X

Weller, 1993, MK-801 and memantine protect cultured neurons from glutamate toxicity induced by glutamate carboxypeptidase-mediated cleavage of methotrexate, Eur. J. Pharmacol. Environ. Toxicol., 248, 303, 10.1016/0926-6917(93)90004-A

Wenk, 1994, Investigations of neurotoxicity and neuroprotection within the nucleus basalis of the rat, Brain Res., 655, 7, 10.1016/0006-8993(94)91590-3

Wenk, 1995, MK-801, memantine and amantadine show neuroprotective activity in the nucleus basalis magnocellularis, Eur. J. Pharmacol. Environ. Toxicol., 293, 267, 10.1016/0926-6917(95)00028-3

Wenk, 1996, The effects of mitochondrial failure upon cholinergic toxicity in the nucleus basalis, Neuroreport, 7, 1453, 10.1097/00001756-199606170-00001

Wenk, 1998, Potential therapies for a novel animal model of Alzheimer’s disease-chronic neuroinflammation of transgenic rats that overexpress human-amyloid, Neurobiol. Aging, 19, 544

Wenk, 1997, Neuroprotection of acetylcholinergic basal forebrain neurons by memantine and neurokinin B, Behav. Brain Res., 83, 129, 10.1016/S0166-4328(97)86056-1

Wenzel, 1995, Distribution of NMDA receptor subunit proteins NR2A, 2B, 2C and 2D in rat brain, Neuroreport, 7, 45, 10.1097/00001756-199512000-00010

Wesemann, 1979, In vitro studies on the possible effects of 1-aminoadamantanes on the serotonergic system in M. Parkinson, J. Neural Transm. Gen. Sect., 44, 263, 10.1007/BF01250322

Wesemann, 1982, Effect of 1-aminoadamantanes on the MAO activity in brain, liver, and kidney of the rat, Arzneim. Forsch. Drug Res., 32, 1241

Wesemann, 1981, Effect of 1-aminoadamantanes on adenine nucleotide and serotonin storage in blood platelets, Eur. J. Cell Biol., 26, 158

Wesemann, 1982, Distribution of memantine in brain, liver, and blood of the rat, Arzneim. Forsch. Drug Res., 32, 1243

Wesemann, 1983, On the pharmacodynamics and pharmacokinetics of memantine, Arzneim. Forsch. Drug Res., 33, 1122

Wesemann, W., Sturm, G. Funfgeld, E.W., 1980. Distribution of metabolism of the potential anti-Parkinson drug memantine in the human. J. Neural Transm. 16, Suppl. 143–148.

Wesemann, 1979, 5-Hydroxytryptamine and ATP-storing organelles in nucleated thrombrocytes. Morphological and biochemical studies on spindle cells of the duck, Eur. J. Cell Biol., 19, 26

Wesemann, 1981, 5-Hydroxytryptamine and adenine uptake by human blood platelets following the release reaction, Thromb. Res., 21, 367, 10.1016/0049-3848(81)90137-7

Yamakura, 1993, Different sensitivities of NMDA receptor channel subtypes to non-competitive antagonists, Neuroreport, 4, 687, 10.1097/00001756-199306000-00021

Yenari, 1998, Dose escalation safety and tolerance study of the competitive NMDA antagonist Selfotel (CGS 19755) in neurosurgery patients, Clin. Neuropharmacol., 21, 28

Youssif, 1986, Potentiation of the locomotor activity of memantine by aminophylline, Arzneim. Forsch. Drug Res., 36, 1717

Zajaczkowski, 1997, Uncompetitive NMDA receptor antagonists attenuate NMDA-induced impairment of passive avoidance learning and LTP, Neuropharmacology, 36, 961, 10.1016/S0028-3908(97)00070-1

Zajaczkowski, 1996, Discriminative stimulus effects of the NMDA receptor antagonists MK-801 and CGP 37849 in rats, Pharmacol. Biochem. Behav., 55, 163, 10.1016/0091-3057(95)02290-2

Zajaczkowski, 1996, Infusion of (+)-MK-801 and memantine—contrasting effects on radial maze learning in rats with entorhinal cortex lesion, Eur. J. Pharmacol., 296, 239, 10.1016/0014-2999(95)00716-4

Zhong, 1995, Expression of mRNAs encoding subunits of the NMDA receptor in developing rat brain, J. Neurochem., 64, 531, 10.1046/j.1471-4159.1995.64020531.x