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

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.