Cerebroprotective properties of SM-20220, a potent Na(+)/H(+) exchange inhibitor, in transient cerebral ischemia in rats.
The aim of this study was to investigate the contribution of the Na(+)/H(+) exchanger to cerebral ischemia using SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate), a newly synthesized compound. In in vitro experiments, we evaluated the inhibitory effect of SM-20220 on the Na(+)/H(+) exchanger in cultured neurons and glial cells. The IC(50) of SM-20220 in neurons and glial cells was 5 nM and 20 nM, respectively. To examine the in vivo effects of SM-20220 on brain injury, we used a transient middle cerebral artery occlusion model in rats. SM-20220 given intravenously 1 h after occlusion significantly reduced the extent of cerebral edema, Na(+) content and infarcted area in a dose-dependent manner. The results of the present study suggest that the Na(+)/H(+) exchanger is involved in the aggravation of brain edema and infarction, and its inhibitor may exert protective effects on post-ischemic brain damage.
Kuribayashi
Y
Y
Sumitomo Pharmaceuticals Research Center, 1-98, Kasugadenaka 3-chome, Konohana-ku, Osaka, Japan.
Itoh
N
N
Kitano
M
M
Ohashi
N
N
D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D001834:Body Water / Q000378:metabolism; D001929:Brain Edema / Q000378:metabolism / Q000517:prevention & control; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000378:metabolism / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000577:Amides; D004791:Enzyme Inhibitors; D007211:Indoles; D018696:Neuroprotective Agents; C401341:SM 20220; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium