Cerebroprotective properties of SM-20220, a potent Na(+)/H(+) exchange inhibitor, in transient cerebral ischemia in rats.

Abstract

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.

• Authors: Y Kuribayashi, N Itoh, M Kitano, N Ohashi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 383 Issue 2 Pg. 163-8 (Oct 27 1999) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10585530 (Publication Type: Journal Article)

Chemical References

• Amides
• Enzyme Inhibitors
• Indoles
• Neuroprotective Agents
• SM 20220
• Sodium-Hydrogen Exchangers
• Sodium

Topics

• Amides (therapeutic use)
• Animals
• Body Water (metabolism)
• Brain Edema (metabolism, prevention & control)
• Cells, Cultured
• Cerebral Infarction (metabolism, prevention & control)
• Enzyme Inhibitors (therapeutic use)
• Hydrogen-Ion Concentration
• Indoles (therapeutic use)
• Ischemic Attack, Transient (drug therapy, enzymology)
• Male
• Neuroglia (drug effects, enzymology)
• Neurons (drug effects, enzymology)
• Neuroprotective Agents (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Rats, Wistar
• Sodium (metabolism)
• Sodium-Hydrogen Exchangers (antagonists & inhibitors, metabolism)