Functional proteins involved in regulation of intracellular Ca(2+) for drug development: pharmacology of SEA0400, a specific inhibitor of the Na(+)-Ca(2+) exchanger.

Abstract

The Na(+)-Ca(2+) exchanger (NCX) is involved in regulation of intracellular Ca(2+) concentration. A specific inhibitor of NCX has been required for clarification of the physiological and pathological roles of NCX. We have developed 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a highly potent and selective inhibitor of NCX. SEA0400 in the concentration range that inhibits NCX exhibits negligible affinities for the Ca(2+) channels, Na(+) channels, K(+) channels, noradrenaline transporter, and 14 receptors; and it does not affect the activities of the store-operated Ca(2+) channel, Na(+)-H(+) exchanger, and several enzymes including Na(+),K(+)-ATPase and Ca(2+)-ATPase. Furthermore, recent studies show that SEA0400 attenuates ischemia-reperfusion injury in the brain, heart, and kidney and radiofrequency lesion-induced edema in rat brain. These findings suggest that NCX plays a key role in ischemia-reperfusion injury and may be a target molecule for treatment of reperfusion injury-related diseases.

• Authors: Toshio Matsuda, Yutaka Koyama, Akemichi Baba
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 97 Issue 3 Pg. 339-43 (Mar 2005) ISSN: 1347-8613 [Print] Japan
• PMID: 15764845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Aniline Compounds
• Phenyl Ethers
• SEA 0400
• Sodium-Calcium Exchanger
• Calcium

Topics

• Aniline Compounds (chemistry, pharmacology)
• Animals
• Calcium (metabolism)
• Drug Design
• Models, Biological
• Molecular Structure
• Myocardial Reperfusion Injury (physiopathology, prevention & control)
• Phenyl Ethers (chemistry, pharmacology)
• Rats
• Sodium-Calcium Exchanger (antagonists & inhibitors)