Identification of <i>R</i>(−)‐isomer of efonidipine as a selective blocker of T‐type Ca²⁺ channels

• Taiji Furukawa

• Reiko Miura

• Mitsuyoshi Honda

• Natsuko Kamiya

• Yasuo Mori

• Satoshi Takeshita

• Takaaki Isshiki

• Toshihide Nukada

抄録

<jats:list list-type="explicit-label"> Efonidipine, a derivative of dihydropyridine Ca 2+ antagonist, is known to block both L‐ and T‐type Ca 2+ channels. It remains to be clarified, however, whether efonidipine affects other voltage‐dependent Ca 2+ channel subtypes such as N‐, P/Q‐ and R‐types, and whether the optical isomers of efonidipine have different selectivities in blocking these Ca 2+ channels, including L‐ and T‐types. To address these issues, the effects of efonidipine and its R (−)‐ and S (+)‐isomers on these Ca 2+ channel subtypes were examined electrophysiologically in the expression systems using Xenopus oocytes and baby hamster kidney cells (BHK tk‐ts13). Efonidipine, a mixture of R (−)‐ and S (+)‐isomers, exerted blocking actions on L‐ and T‐types, but no effects on N‐, P/Q‐ and R‐type Ca 2+ channels. The selective blocking actions on L‐ and T‐type channels were reproduced by the S (+)‐efonidipine isomer. By contrast, the R (−)‐efonidipine isomer preferentially blocked T‐type channels. The blocking actions of efonidipine and its enantiomers were dependent on holding potentials. These findings indicate that the R (−)‐isomer of efonidipine is a specific blocker of the T‐type Ca 2+ channel. British Journal of Pharmacology (2004) 143 , 1050–1057. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0705944">10.1038/sj.bjp.0705944

収録刊行物

• British Journal of Pharmacology

  British Journal of Pharmacology 143 (8), 1050-1057, 2004-12

  Wiley

キーワード

• Pharmacology

詳細情報

• CRID: 1363951793592729600
• NII論文ID: 30022967404
• DOI: 10.1038/sj.bjp.0705944
• ISSN: 14765381
• ISSN: 00071188
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Fsj.bjp.0705944
• Web Site: https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0705944
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