Mibefradil (dihydrochloride)

Mibefradil dihydrochloride (Ro 40-5967 dihydrochloride) is a calcium channel blocker with moderate selectivity for T-type Ca²⁺ channels (IC₅₀s of 2.7 μM and 18.6 μM for T-type and L-type currents, respectively)^[1]. IC50 & Target:IC50: 2.7 μM (T-type calcium channel), 18.6 μM (L-type calcium channel)^[1] In Vitro: Mibefradil dihydrochloride inhibits reversibly the T- and L-type currents with IC₅₀ values of 2.7 and 18.6 μM, respectively. The inhibition of the L-type current is voltage-dependent, whereas that of the T-type current is not. Ro 40-5967 blocks T-type current already at a holding potential of -100 mV^[1] At a higher concentration (20 μM), Mibefradil reduces the amplitude of excitatory junction potentials (by 37±10 %), slows the rate of repolarisation (by 44±16 %) and causes a significant membrane potential depolarisation (from 83±1 mV to 71±5 mV). At a higher Mibefradil concentration (20 μM) there is significant membrane potential depolarisation and a slowing of repolarisation. These actions of Mibefradil are consistent with K⁺ channel inhibition, which has been shown to occur in human myoblasts and other cells^[2]. In Vivo: The hearing thresholds of the 24-26 week old C57BL/6J mice differ following the 4-week treatment period. The hearing threshold at 24 kHz is significantly decreased in the Mibefradil-treated and benidipine-treated groups compared with the saline-treated group (P<0.05)^[3]. Compared with the saline-treated group, rats receiving Mibefradil or NSC 64013 show significant lower Ca_V3.2 expression in the spinal cord and DRG^[4].