Neuroprotective activity of CHF3381, a putative N-methyl-D-aspartate receptor antagonist.
The aim of this study was to evaluate the neuroprotective effect of CHF3381, a novel putative NMDA antagonist characterized by a good therapeutic index. We have compared the effects of CHF3381 on kainate seizure-induced neurodegeneration with those produced by the non competitive NMDA receptor antagonist MK-801 and by the Na channel blocker lamotrigine. All compounds have been employed at doses incapable of preventing or attenuating seizures. The fluorescent marker Fluoro-Jade B has been used to identify degenerating cells. Animals pretreated with lamotrigine presented the same degree of cell damage as the controls. As for the controls, a clear correlation was also observed between seizure severity and neurodegeneration. In contrast, MK-801 and CHF3381 completely prevented cell damage. These data indicate that CHF3381 may be successfully utilized in neurological disorders characterized by or associated with neurodegenerative excitotoxicity.
Zucchini
Silvia
S
Department of Clinical and Experimental Medicine, Section of Pharmacology Neuroscience Center, University of Ferrara, via Fossato di Mortara, 17-19, 44100 Ferrara, Italy.
Buzzi
Andrea
A
Bergamaschi
Marco
M
Pietra
Claudio
C
Villetti
Gino
G
Simonato
Michele
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D006652:Histological Techniques; D007189:Indans / Q000494:pharmacology*; D007608:Kainic Acid; D000077213:Lamotrigine; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D014227:Triazines / Q000494:pharmacology
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D014227:Triazines; D016291:Dizocilpine Maleate; D007608:Kainic Acid; D005998:Glycine; D000077213:Lamotrigine; C431890:indantadol