Identification of R(-)-isomer of efonidipine as a selective blocker of T-type Ca2+ channels.
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.
Furukawa
Taiji
T
Department of Internal Medicine, Teikyo University School of Medicine 2-11-1 Kaga, Itabashi-ku, Tokyo 173-0003, Japan. tfrkw@med.teikyo-u.ac.jp
Miura
Reiko
R
Honda
Mitsuyoshi
M
Kamiya
Natsuko
N
Mori
Yasuo
Y
Takeshita
Satoshi
S
Isshiki
Takaaki
T
Nukada
Toshihide
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D004095:Dihydropyridines / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009596:Nitrophenols / Q000737:chemistry* / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D014981:Xenopus
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine