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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Mibefradil dihydrochloride (Ro 40-5967; trade name: Posicor), the dihydrochloride salt of miberfradil, is a CCB/calcium channel blocker with anti-hypertensive activity. It has 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. It is an approved drug for the treatment of hypertension and chronic angina pectoris.
Targets |
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ln Vitro |
T-type and L-type currents are reversibly inhibited by mibefradil dihydrochloride, with IC50 values of 2.7 and 18.6 μM, respectively. While T-type current suppression is independent of voltage, L-type current suppression is reliant on voltage. The T-shaped current is already blocked by Ro 40-5967 at a holding potential of -100 mV [1]. Mibefradil significantly depolarized the membrane potential (from -83±1 mV to -71±5 mV) at higher concentrations (20 μM), decreased the repolarization rate (44±16%), and lowered the amplitude of the excitatory junction potential (37±10%). The membrane potential exhibits a notable depolarization and repolarization slowdown at higher concentrations of Mibefradil dihydrochloride (20 μM). The observed effects of Mibefradil align with the evidence of K+ channel blockage in human myoblasts and other cell types [2].
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ln Vivo |
Following a 4-week treatment period, hearing thresholds in C57BL/6J mice aged 24 to 26 weeks varied. The 24 kHz hearing threshold of both the benidipine- and Mibefradil dihydrochloride-treated groups was considerably (P<0.05) lower than that of the saline-treated group[3]. The expression of CaV3.2 in the DRG and spinal cord of rats in the Mibefradil dihydrochloride or NSC 64013 group was considerably lower than in the normal saline group [4].
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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.
[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 |
Molecular Formula |
C29H40CL2FN3O3
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Molecular Weight |
568.5506
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CAS # |
116666-63-8
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Related CAS # |
Mibefradil;116644-53-2;Mibefradil dihydrochloride hydrate;1049728-52-0
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SMILES |
Cl[H].Cl[H].FC1C([H])=C([H])C2=C(C=1[H])C([H])([H])C([H])([H])[C@](C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C1=NC3=C([H])C([H])=C([H])C([H])=C3N1[H])([C@@]2([H])C([H])(C([H])([H])[H])C([H])([H])[H])OC(C([H])([H])OC([H])([H])[H])=O
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
H2O : ~150 mg/mL (~263.83 mM)
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.