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

Efonidipine, a derivative of dihydropyridine Ca2+ antagonist, is known to block both L- and T-type Ca2+ channels. It remains to be clarified, however, whether efonidipine affects other voltage-dependent Ca2+ channel subtypes such as N-, P/Q- and R-types, and whether the optical isomers of efonidipine have different selectivities in blocking these Ca2+ channels, including L- and T-types. To address these issues, the effects of efonidipine and its R(−)- and S(+)-isomers on these Ca2+ 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 Ca2+ 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 Ca2+ channel. British Journal of Pharmacology (2004) 143, 1050–1057. doi:10.1038/sj.bjp.0705944