A selective T-type Ca2+ channel blocker R(-) efonidipine

Min Chul Shin, Chang Ju Kim, Byung Il Min, Sachie Ogawa, Eiichiro Tanaka, Norio Akaike

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Recently, novel compound R(-) efonidipine was reported to selectively block low-voltage-activated (LVA or T-type) Ca2+ channels in peripheral organs. We examined how R(-) efonidipine acts on T-type and high-voltage- activated (HVA) Ca2+ channels in mammalian central nervous system (CNS) neurons. Furthermore, we compared the effects of R(-) efonidipine with those of flunarizine and mibefradil on both T-type and HVA Ca2+ channels in rat hippocampal CA1 neurons by using the nystatin perforated-patch clamp technique. Flunarizine and mibefradil nonselectively inhibited both T-type and HVA Ca2+ channels, though the dose-dependent blocking potency of flunarizine on T-type Ca2+ channels was slightly stronger than that of mibefradil. In contrast, R(-) efonidipine inhibited only T-type Ca 2+ channels and did not show any effect on HVA Ca2+ channels. The inhibitory actions of R(-) efonidipine or flunarizine were similar on both Ba2+ and Ca2+ current components passing through T-type Ca2+ channels. In addition, flunarizine but not R(-) efonidipine inhibited voltage-dependent Na+ channels and Ca 2+-activated K+ channels. Thus, it appears that R(-) efonidipine is a selective blocker for T-type Ca2+ channels. It could be used as a pharmacological tool in future studies on T-type Ca2+ channels.

Original languageEnglish (US)
Pages (from-to)411-421
Number of pages11
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume377
Issue number4-6
DOIs
StatePublished - Jun 1 2008

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Flunarizine
Mibefradil
Neurons
Nystatin
Patch-Clamp Techniques
efonidipine
Central Nervous System
Pharmacology

Keywords

  • Ca channels
  • Hippocampal CA1 neuron
  • R(-) efonidipine
  • T-type

ASJC Scopus subject areas

  • Pharmacology

Cite this

A selective T-type Ca2+ channel blocker R(-) efonidipine. / Shin, Min Chul; Kim, Chang Ju; Min, Byung Il; Ogawa, Sachie; Tanaka, Eiichiro; Akaike, Norio.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 377, No. 4-6, 01.06.2008, p. 411-421.

Research output: Contribution to journalArticle

Shin, Min Chul ; Kim, Chang Ju ; Min, Byung Il ; Ogawa, Sachie ; Tanaka, Eiichiro ; Akaike, Norio. / A selective T-type Ca2+ channel blocker R(-) efonidipine. In: Naunyn-Schmiedeberg's Archives of Pharmacology. 2008 ; Vol. 377, No. 4-6. pp. 411-421.
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