Mibefradil is a calcium channel antagonist which can block both T-type and L-type calcium channels and the IC50 of Mibefradil for T-type and L-type calcium current are 0.7μM and 2μM, respectively [1, 2]. Mibefradil is clinically used to treat hypertension, chronic stable angina pectoris [1] and ovarian, pancreas, glioblastoma multiforme tumors [3].
Mibefradil (100μM) significantly inhibited thapsigargin-induced endoplasmic reticulum Ca2+ release in EA.hy926 cells and HK-2 cells; Mibefradil (100μM; 24h) significantly inhibited the proliferation of HK-2 and EA.hy926 cells [4]. Mibefradil (5μM; 30h) decreased myoblast fusion [2]. Mibefradil (0~10μM; 48h) suppressed the cell viability of both MOLT-4 and Jurkat in a dose-dependent manner; Mibefradil (0, 5,10μM; 48h) enhanced the percentage of MOLT-4 cells in the G0/G1 and sub-G1 phase and reduced that in the S phase [3].
Mibefradil (15mg/kg; 3d; b.i.d.; i.p.) caused a profound reduction of fasting blood glucose in male db/db mice[5]. Mibefradil (20, 40mg/kg; i.p.) decreased the productions of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) of male BALB/c mice stimulated by lipopolysaccharide (LPS) [6]. Mibefradil (20mg/kg; 6months; p.o.) reduced the glomerulosclerosis and tubulointerstitial injury of Sprague-Dawley rats which were induced diabetes by strepozotocin [7].
References:
[1] Abernethy D R. Pharmacologic and pharmacokinetic profile of mibefradil, a T- and L-type calcium channel antagonist [J]. The American journal of cardiology, 1997, 80(4b): 4c-11c.
[2] Liu J H, Bijlenga P, Occhiodoro T, et al. Mibefradil (Ro 40-5967) inhibits several Ca2+ and K+ currents in human fusion-competent myoblasts [J]. British journal of pharmacology, 1999, 126(1): 245-250.
[3] Huang W, Lu C, Wu Y, et al. T-type calcium channel antagonists, mibefradil and NNC-55-0396 inhibit cell proliferation and induce cell apoptosis in leukemia cell lines [J]. Journal of experimental & clinical cancer research, 2015, 34(1): 54.
[4] Li P, Rubaiy H N, Chen G L, et al. Mibefradil, a T-type Ca2+ channel blocker also blocks Orai channels by action at the extracellular surface [J]. British journal of pharmacology, 2019, 176(19): 3845-3856.
[5] Lu Y, Long M, Zhou S, et al. Mibefradil reduces blood glucose concentration in db/db mice [J]. Clinics (Sao Paulo, Brazil), 2014, 69(1): 61-67.
[6] Wan L, Wu W, Jiang S, et al. Mibefradil and flunarizine, two T-type calcium channel inhibitors, protect mice against lipopolysaccharide-induced acute lung injury [J]. Mediators of inflammation, 2020, 2020: 3691701.
[7] Ma G, Allen T J, Cooper M E, et al. Calcium channel blockers, either amlodipine or mibefradil, ameliorate renal injury in experimental diabetes [J]. Kidney international, 2004, 66(3): 1090-1098.
Mibefradil是一种钙通道阻断剂，可以阻断T型和L型钙通道，Mibefradil对T型和L型钙电流的IC50分别为0.7μM和2μM[1, 2]。Mibefradil在临床上用于治疗高血压和慢性稳定型心绞痛[1]以及卵巢肿瘤、胰腺肿瘤和多形性胶质母细胞瘤[3]。
Mibefradil（100μM）可以显著抑制毒胡萝卜素诱导的EA.hy926细胞和HK-2细胞内质网Ca2+的释放；Mibefradil（100μM；24h）可以显著抑制HK-2和EA.hy926细胞的增殖[4]。Mibefradil（5μM；30h）减少肌细胞融合[2]。Mibefradil（0~10μM；48h）以剂量依赖的方式抑制MOLT-4和Jurkat的细胞活力；Mibefradil（0、5、10μM；48h）使G0/G1期和亚G1期的MOLT-4细胞百分比升高，S期的百分比降低[3]。
Mibefradil（15mg/kg；3d；b.i.d.；i.p.）导致雄性db/db小鼠的空腹血糖大幅降低[5]。Mibefradil（20、40mg/kg；i.g.）可降低LPS（lipopolysaccharide）刺激的雄性BALB/c小鼠BALF（bronchoalveolar lavage fluid）中TNF-α和IL-6的产生[6]。Mibefradil（20mg/kg；6months；p.o.）可减轻链脲佐菌素诱导的糖尿病Sprague-Dawley大鼠的肾小球硬化和肾小管间质损伤[7]。