Abstract
Glutamate may act via an N-methyl-D-Aspartate (NMDA)-sensitive receptor site to destroy cholinergic neurons within the nucleus basalis magnocellularis in age-associated neurodegenerative diseases. Multiple interesting properties of the NMDA receptor are relevant to its excitotoxic actions, e.g., glutamate is ineffective unless a glycine (gly) modulatory site is also occupied. Thus, the antagonism of glutamate receptor-related toxicity by blockade of either the NMDA-sensitive recognition site or the gly binding site may therefore have therapeutic applications. The current study investigated the ability of four novel noncompetitive antagonists at these two sites: one NMDA open channel antagonist (MRZ 2/579: 1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride), and three glyB receptor antagonists (MRZ 2/570: 8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridaziono [4,5-beta] quinoline-5-oxide choline salt; MRZ 2/57: 8-fluoro-4-hydroxy-1-oxo-1,2-dihydropyridaziono [4,5-beta] quinoline-5-oxide choline; MRZ 2/576: 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridaziono [4,5-beta] quinoline-5-oxide choline) administered acutely, to provide neuroprotection from a NMDA receptor agonist within the nucleus basalis magnocellularis of young rats. Injecti...Continue Reading
References
Apr 1, 1992·Neurology·R L Albin, J T Greenamyre
May 11, 1992·Annals of the New York Academy of Sciences·S M Rothman
Apr 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·A Frandsen, A Schousboe
Feb 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J E Huettner, B P Bean
Sep 1, 1989·Neurobiology of Aging·J T Greenamyre, A B Young
Aug 12, 1988·Science·N W Kleckner, R Dingledine
Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J A KempG N Woodruff
Nov 1, 1969·The Biochemical Journal·F Fonnum
Jan 1, 1981·Annual Review of Pharmacology and Toxicology·J C Watkins, R H Evans
Feb 2, 1984·Nature·L NowakA Prochiantz
Sep 1, 1995·Annals of Neurology·M F Beal
Jun 1, 1994·Neuroscience·D D RasmussonJ C Szerb
Jan 1, 1996·Experimental Neurology·J G GreeneJ T Greenamyre
Oct 6, 1995·European Journal of Pharmacology·G L WenkS L Mobley
Jun 17, 1996·Neuroreport·G L WenkD D Roice
Jan 1, 1996·Neuropharmacology·T PriestleyJ A Kemp
Jul 1, 1997·Neuroscience and Biobehavioral Reviews·W DanyszG Quack
Citations
Mar 7, 2006·Biogerontology·Anil K ManthaNajma Z Baquer
May 9, 2000·Brain Research·Y LiuM D Ginsberg
Apr 8, 1999·Neuropharmacology·C G ParsonsG Quack
Jul 18, 2008·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Stephen SallowayJeffrey L Cummings
Jan 5, 2001·Expert Opinion on Investigational Drugs·M E Tranquillini, A Reggiani
Feb 22, 2005·Neuropharmacology·Wojciech DanyszPiotr Popik
May 1, 2009·Expert Review of Clinical Pharmacology·Gerhard Rammes