Mechanism underlying the block of human Cav3.2 T-type Ca2+ channels by benidipine, a dihydropyridine Ca2+ channel blocker

T-type calcium channel blockers – new and notable

“…S(+) enantiomer had similar effect on both channels at both HPs (Furukawa et al 2004). More effective was efonidipine in inhibition of the Ca V 3.2 channel in HEK 293 cells with an IC 50 of 240 nM at a HP -90 mV (Inayoshi et al 2011). Benidipine blocked the Ca V 3.2 channel expressed in HEK 293 cells with an IC 50 140 nM (Inayoshi et al 2011).…”

“…Benidipine blocked the Ca V 3.2 channel expressed in HEK 293 cells with an IC 50 140 nM (Inayoshi et al 2011). (S, S) benidipine was slightly better blocker (IC 50 = 40 nM) than (R, R) benidipine (IC 50 = 146 nM) (Inayoshi et al 2011).…”

“…More effective was efonidipine in inhibition of the Ca V 3.2 channel in HEK 293 cells with an IC 50 of 240 nM at a HP -90 mV (Inayoshi et al 2011). Benidipine blocked the Ca V 3.2 channel expressed in HEK 293 cells with an IC 50 140 nM (Inayoshi et al 2011). (S, S) benidipine was slightly better blocker (IC 50 = 40 nM) than (R, R) benidipine (IC 50 = 146 nM) (Inayoshi et al 2011).…”

“…Benidipine seems to be more selective T-type calcium channel blocker as the half-maximal blocking concentration for the Ca V 1.2 channel was 14 µM (Furukawa et al 1999), i.e., 100-fold higher than the half-maximal inhibitory concentration for the Ca V 3.2 channel (Inayoshi et al 2011). Still such claim should be taken with certain caution as the former was measured in Xenopus oocytes while the later was measured in mammalian (HEK 293) cell line.…”

Enantioselective Pd(II)-Catalyzed Intramolecular Oxidative 6-endoAminoacetoxylation of Unactivated Alkenes

“…Enantiomer-enriched nitrogen-containing heterocycles, such as 3-hydroxypiperidines, are frequently found in pharmaceuticals, agrochemicals and natural products . For instance, Jervine, a steroidal alkaloid, isolated from the Veratrum plant genus, and Benidipine, a dihydropyridine calcium channel blocker for curing hypertension (Scheme a) . Considerable efforts have been therefore directed toward synthesis of chiral heterocycles, and many methods have been developed .…”