SM-20220, a potent Na+/H+ exchange inhibitor, improves consciousness recovery and neurological outcome following transient cerebral ischaemia in gerbils.
We studied the cerebroprotective effect of SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulphonate), a newly synthesized Na+/H+ exchanger (NHE) inhibitor, in Mongolian gerbil global ischaemia. Transient cerebral ischaemia was induced by clipping both common carotid arteries for 30 min followed by 24h reperfusion. Intravenous administration of SM-20220 (0.3 or 1.0 mg kg(-1)) immediately after reperfusion significantly shortened the consciousness recovery time (P < 0.01). SM-20220 also improved the neurological outcome (McGraw's scale) after reperfusion. At the dose of 1.0 mg kg(-1), the mortality rate was significantly reduced at 24 h after reperfusion (P < 0.01). This study shows that NHE is involved in the aggravation of cerebral function, represented by consciousness recovery, and neurological outcome following transient forebrain ischaemia, and that its inhibitor may exert protective effects on post-ischaemic brain damage.
Kuribayashi
Y
Y
Sumitomo Pharmaceuticals Research Center, Osaka, Japan. kyosikaz@sumitomopharm.co.jp
Itoh
N
N
Horikawa
N
N
Ohashi
N
N
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D003243:Consciousness / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D007211:Indoles / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000401:mortality; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012720:Severity of Illness Index; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D015996:Survival Rate; D013997:Time Factors
D000577:Amides; D007211:Indoles; C401341:SM 20220; D017923:Sodium-Hydrogen Exchangers