Neuroprotective action of a novel compound--M50463--in primary cultured neurons.
The neuroprotective effects of a novel synthetic compound, M50463, have been determined by using embryonic rat neocortical neurons in various culture conditions. M50463 was initially characterized as a potent specific ligand for a voltage-dependent sodium channel by radioligand binding studies. In fact, M50463 inhibited neuronal cell death induced by veratrine and inhibited an increase of the intracellular calcium level in neurons evoked by veratrine. In addition to such expected effects, M50463 had the ability to prevent glutamate neurotoxicity, to promote the neuronal survival in serum-deprived medium and to prevent nitric oxide-induced neurotoxicity. These results suggested that M50463 is not a simple sodium channel blocker, but a neuroprotective agent which has some crucial mechanism of action on neuronal death occurring in various situations, and it is a novel, innovative candidate for neuroprotective therapy for various neurodegenerative disorders.
Shimojo
M
M
Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan. mshimojo@mochida.co.jp
Takasugi
K
K
Yamamoto
I
I
Funato
H
H
Mochizuki
H
H
Kohsaka
S
S
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001496:Batrachotoxins / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D018698:Glutamic Acid; D007211:Indoles / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins; D009529:Nicardipine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D014702:Veratrine; D014810:Vitamin E / Q000494:pharmacology