Mibefradil dihydrochloride (Synonyms: Posicor, Ro 405967) |
| Catalog No.GC10218 |
A general calcium channel blocker
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 116666-63-8
Sample solution is provided at 25 µL, 10mM.
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Mibefradil dihydrochloride (Ro 40-5967 dihydrochloride) is a calcium channel blocker with moderate selectivity for T-type Ca2+ channels displaying IC50s of 2.7 μM and 18.6 μM for T-type and L-type currents, respectively.
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].
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 Ethosuximide show significant lower CaV3.2 expression in the spinal cord and DRG[4].
Reference:
[1]. Mehrke G, et al. The Ca(++)-channel blocker Ro 40-5967 blocks differently T-type and L-type Ca++ channels. J Pharmacol Exp Ther. 1994 Dec;271(3):1483-8.
[2]. Brain KL, et al. The sources and sequestration of Ca(2+) contributing to neuroeffector Ca(2+) transients in the mouse vas deferens. J Physiol. 2003 Dec 1;553(Pt 2):627-35.
[3]. Yu YF, et al. Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers. Exp Ther Med. 2016 Mar;11(3):1039-1044.
[4]. Shiue SJ, et al. Chronic intrathecal infusion of T-type calcium channel blockers attenuates CaV3.2 upregulation in nerve-ligated rats. Acta Anaesthesiol Taiwan. 2016 Oct 17. pii: S1875-4597(16)30071-6.
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Animal experiment: |
Mice[3] A total of 30 male C57BL/6J mice (age, 6-8 weeks) are randomized into three groups for the detection of three calcium channel receptor subunits α1G, α1H and α1I, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, a further 30 C57BL/6J male mice (age, 24-26 weeks) are allocated at random into three treatment groups: Saline, Mibefradil and benidipine. Each group is subjected to auditory brainstem recording (ABR) and distortion product otoacoustic emission (DPOAE) tests following treatment. Mibefradil and benidipine are dissolved in physiological saline solution. A preliminary experiment led to the selection of dosages of 30 mg/kg/day Mibefradil and 10 mg/kg/day Benidipine. The drugs are administered to the mice by gavage for four consecutive weeks. Rats[4] Male Sprague-Dawley rats (200-250 g) are used for right L5/6 SNL to induce neuropathic pain. Intrathecal infusion of saline or TCC blockers [Mibefradil (0.7 μg/h) or Ethosuximide (60 μg/h)] is started after surgery for 7 days. Fluorescent immunohistochemistry and Western blotting are used to determine the expression pattern and protein level of CaV3.2. Hematoxylin-eosin and toluidine blue staining are used to evaluate the neurotoxicity of tested agents. |
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References: [1]. Mehrke G, et al. The Ca(++)-channel blocker Ro 40-5967 blocks differently T-type and L-type Ca++ channels. J Pharmacol Exp Ther. 1994 Dec;271(3):1483-8. |
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| Cas No. | 116666-63-8 | SDF | |
| Synonyms | Posicor, Ro 405967 | ||
| Chemical Name | [(1S,2S)-2-[2-[3-(1H-benzimidazol-2-yl)propyl-methylamino]ethyl]-6-fluoro-1-propan-2-yl-3,4-dihydro-1H-naphthalen-2-yl] 2-methoxyacetate;dihydrochloride | ||
| Canonical SMILES | CC(C)C1C2=C(CCC1(CCN(C)CCCC3=NC4=CC=CC=C4N3)OC(=O)COC)C=C(C=C2)F.Cl.Cl | ||
| Formula | C29H40Cl2FN3O3 | M.Wt | 568.55 |
| Solubility | DMF: 16mg/ml, DMSO: 14mg/ml, Ethanol: 16mg/ml, Water: 50mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7589 mL | 8.7943 mL | 17.5886 mL |
| 5 mM | 0.3518 mL | 1.7589 mL | 3.5177 mL |
| 10 mM | 0.1759 mL | 0.8794 mL | 1.7589 mL |
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- Purity: >99.00%
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