Effects of MK-801, dantrolene, and FK506 on convulsive seizures and brain nitric oxide production in seizure-susceptible EL mice.
To clarify the role of nitric oxide (NO) in the pathogenesis of seizures in susceptible EL mice, we investigated effects of three drugs potentially related to NO production, MK-801, dantrolene, and FK506, on convulsive seizures and brain NO metabolites (NOx). MK-801 or dantrolene, but not FK506, suppressed convulsive seizures in EL mice; only MK-801 reduced NOx in the brain. Our results suggested involvement of the N-methyl-D-aspartate receptor-channel complex and intracellular calcium mobilization, but not calcineurin, in the convulsions of EL mice.
Nagatomo
I
I
Department of Neuropsychiatry, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, 890-8520, Kagoshima, Japan. nagatomo@m2.kufm.kagoshimak-u.ac.jp  
Hashiguchi
W
W
Tominaga
M
M
Akasaki
Y
Y
Uchida
M
M
Takigawa
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003620:Dantrolene / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D051379:Mice; D008815:Mice, Inbred Strains; D009125:Muscle Relaxants, Central / Q000008:administration & dosage; D009566:Nitrates / Q000032:analysis / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000032:analysis / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016559:Tacrolimus / Q000008:administration & dosage*
D018691:Excitatory Amino Acid Antagonists; D007166:Immunosuppressive Agents; D009125:Muscle Relaxants, Central; D009566:Nitrates; D009573:Nitrites; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D019703:Calcineurin; D003620:Dantrolene; D002118:Calcium; D016559:Tacrolimus