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.