A novel class of amino-alkylcyclohexanes as uncompetitive, fast, voltage-dependent, N-methyl-D-aspartate (NMDA) receptor antagonists - In vitro characterization

Journal of Neural Transmission

Volumn 114, Issue 12, 2007, Pages 1529-1537

  Gilling, K ^a   Jatzke, C ^a   Wollenburg, C ^a   Vanejevs, M ^b   Kauss, V ^b   Jirgensons, A ^b   Parsons, C G ^a  

^a MERZ PHARMACEUTICALS GMBH   (Germany)

^b LATVIAN INSTITUTE OF ORGANIC SYNTHESIS   (Latvia)

Author keywords

Hippocampal neurons; Kinetics; Memantine; N methyl D aspartate NMDA; Neramexane; Patch clamp; Potency; Selectivity; Voltage dependency

Indexed keywords

1 ETHENYL 3,3,5,5 TETRAMETHYLCYCLOHEXYLAMINE; 1,3,3,5 TETRAMETHYL 6 AZABICYCLO[3.2.1]OCTANE; 8,8,10,10 TETRAMETHYL 1 AZASPIRO[5.5]UNDECANE; CYCLOHEXYLAMINE DERIVATIVE; DIZOCILPINE; MEMANTINE; MRZ 2 1010; MRZ 2 1013; MRZ 2 759; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NERAMEXANE; TRITIUM; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BEHAVIOR DISORDER; BINDING AFFINITY; BRAIN MEMBRANE; BRAIN NERVE CELL; CONTROLLED STUDY; DRUG EFFICACY; DRUG INDICATION; DRUG MECHANISM; DRUG RECEPTOR BINDING; EMBRYO; FEMALE; HIPPOCAMPUS; IN VITRO STUDY; NEUROPHARMACOLOGY; NONHUMAN; PHARMACODYNAMICS; PRIORITY JOURNAL; RAT; RECEPTOR BLOCKING;

ANIMALS; AZA COMPOUNDS; AZABICYCLO COMPOUNDS; BINDING, COMPETITIVE; CELLS, CULTURED; CYCLOHEXYLAMINES; CYCLOPENTANES; DOSE-RESPONSE RELATIONSHIP, DRUG; EXCITATORY AMINO ACID ANTAGONISTS; HIPPOCAMPUS; INHIBITORY CONCENTRATION 50; MEMANTINE; MEMBRANE POTENTIALS; NEURONS; PATCH-CLAMP TECHNIQUES; RATS; RECEPTORS, N-METHYL-D-ASPARTATE; SPIRO COMPOUNDS;

EID: 36749038222     PISSN: 03009564     EISSN: 14351463     Source Type: Journal    
DOI: 10.1007/s00702-007-0792-7     Document Type: Article

References (20)

1. BA Chizh PM Headley 2005 NMDA antagonists and neuropathic pain - multiple drug targets and multiple uses Curr Pharm Des 11 2977 2994
2. W Danysz CG Parsons 1998 Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications Pharmacol Rev 50 597 664
3. W Danysz CG Parsons 2002 Neuroprotective potential of ionotropic glutamate receptor antagonists - II Neurotox Res 4 119 126
4. W Danysz CG Parsons 2003 The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease preclinical evidence Int J Geriatr Psychiatry 18 S23 S32
5. W Danysz CG Parsons A Jirgensons V Kauss J Tillner 2002 Amino-alkyl-cyclohexanes as a novel class of uncompetitive NMDA receptor antagonists Curr Pharm Des 8 835 843
6. R Dingledine K Borges D Bowie SF Traynelis 1999 The glutamate receptor ion channels Pharmacol Rev 51 7 61
7. F Gardoni M Di Luca 2006 New targets for pharmacological intervention in the glutamatergic synapse Eur J Pharmacol 545 1 2 10
8. JW Johnson SE Kotermanski 2006 Mechanism of action of memantine Curr Opin Pharmacol 6 61 67
9. IE Leppik K Marienau NM Graves CA Rask 1988 MK-801 for epilepsy: a pilot study Neurology 38 Suppl 1 405
10. SA Lipton 2006 Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond Nat Rev Drug Discov 5 2 160 170
11. JM Loftis A Janowsky 2003 The N-methyl-D-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications Pharmacol Ther 97 55 85
12. CG Parsons 2001 NMDA receptors as targets for drug action in neuropathic pain Eur J Pharmacol 429 71 78
13. CG Parsons W Danysz G Quack 1998 Glutamate in CNS disorders as a target for drug development: an update Drug News Perspect 11 523 569
14. CG Parsons W Danysz A Bartmann P Spielmanns T Frankiewicz M Hesselink B Eilbacher G Quack 1999a 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 85 108
15. CG Parsons W Danysz G Quack 1999b Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist - a review of preclinical data Neuropharmacology 38 735 767
16. B Reisberg R Doody A Stoffler F Schmitt S Ferris HJ Mobius 2003 Memantine in moderate-to-severe Alzheimer's disease N Engl J Med 348 1333 1341
17. MA Rogawski GL Wenk 2003 The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease CNS Drug Rev 9 275 308
18. S Sveinbjornsdottir JWAS Sander D Upton PJ Thompson PN Patsalos D Hirt M Emre D Lowe JS Duncan 1993 The excitatory amino acid antagonist d-CPP-ene (sdz eaa-494) in patients with epilepsy Epilepsy Res 16 165 174
19. PN Tariot MR Farlow GT Grossberg SM Graham S McDonald I Gergel 2004 Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial JAMA 291 317 324
20. HJ Tuominen J Tiihonen K Wahlbeck 2005 Glutamatergic drugs for schizophrenia: a systematic review and meta-analysis Schizophr Res 72 225 234