米贝地尔

概述用途生物活性靶点体外研究体内研究米贝地尔试剂级价格

米贝地尔

CAS号:116644-53-2
英文名:MIBEFRADIL DIHYDROCHLORIDE
中文名:米贝地尔
CBNumber:CB2399511
分子式:C29H38FN3O3
分子量:495.63
MOL File:116644-53-2.mol

米贝地尔化学性质

熔点 :125 - 130°C
沸点 :647.6±55.0 °C(Predicted)
密度 :1.18±0.1 g/cm3(Predicted)
储存条件 :Desiccate at RT
溶解度 :DMSO (Slightly), Methanol (Slightly)
酸度系数(pKa) :11.93±0.10(Predicted)
形态 :Solid
颜色 :Off-White

米贝地尔性质、用途与生产工艺

概述米贝地尔为四氢萘酚衍生物，其结构与作用明显不同于目前的钙通道拮抗药苯并噻氮卓类以及二氢吡啶类。
用途盐酸米贝地尔主要阻滞T-型钙通道，而不是L-型钙通道。盐酸米贝地尔作用途径与常用钙通道拮抗药既相同又相异。当T-型钙通道被完全抑制后，亦可抑制L-型钙通道。盐酸米贝地尔的受体结合点与维拉帕米、地尔硫卓虽有交叉，但不影响二氢吡啶类（如硝苯地平等）药物的结合。其血管系统选择性与二氢吡啶类药物相似。
生物活性 Mibefradil (Ro 40-5967) 是一种钙离子通道 (calcium channel) 阻断剂，选择性作用于 T 型 Ca2+通道，作用于 T 型和 L 型通道，IC50 分别为 2.7 μM 和 18.6 μM。
靶点

IC50: 2.7 μM (T-type calcium channel), 18.6 μM (L-type calcium channel)
体外研究

Mibefradil inhibits reversibly the T- and L-type currents with IC ₅₀ 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 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.
体内研究

The hearing thresholds of the 24-26 week old C57BL/6J mice differed 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). Compared with the saline-treated group, rats receiving Mibefradil or Ethosuximide show significant lower Ca _V 3.2 expression in the spinal cord and DRG.