Identification of R(-)-isomer of Efonidipine As a Selective Blocker of T-type Ca2+ Channels

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2004 Nov 17

PMID 15545287

Citations 18

Authors

Taiji Furukawa

Reiko Miura

Mitsuyoshi Honda

Natsuko Kamiya

Yasuo Mori

Satoshi Takeshita

Takaaki Isshiki

Toshihide Nukada

Affiliations

Soon will be listed here.

Abstract

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.

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