CAS 116666-63-8|Mibefradil dihydrochloride
Introduction：Basic information about CAS 116666-63-8|Mibefradil dihydrochloride, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | Mibefradil dihydrochloride | ||
|---|---|---|---|
| CAS Number | 116666-63-8 | Molecular Weight | 568.551 |
| Density | / | Boiling Point | 647.6ºC at 760mmHg |
| Molecular Formula | C29H40Cl2FN3O3 | Melting Point | / |
| MSDS | ChineseUSA | Flash Point | 345.5ºC |
Names
| Name | Mibefradil dihydrochloride hydrate |
|---|---|
| Synonym | More Synonyms |
Mibefradil dihydrochloride BiologicalActivity
| Description | Mibefradil 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. |
|---|---|
| Related Catalog | Signaling Pathways >>Membrane Transporter/Ion Channel >>Calcium ChannelResearch Areas >>Cardiovascular Disease |
| Target | IC50: 2.7 μM (T-type calcium channel), 18.6 μM (L-type calcium channel)[1] |
| In Vitro | 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]. |
| In Vivo | 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]. |
| Animal Admin | 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. |
| 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. |
Chemical & Physical Properties
| Boiling Point | 647.6ºC at 760mmHg |
|---|---|
| Molecular Formula | C29H40Cl2FN3O3 |
| Molecular Weight | 568.551 |
| Flash Point | 345.5ºC |
| Exact Mass | 567.243103 |
| PSA | 67.45000 |
| LogP | 6.87490 |
| Vapour Pressure | 1.17E-16mmHg at 25°C |
| InChIKey | MTJLQTFHJIHXIX-GDUXWEAWSA-N |
| SMILES | COCC(=O)OC1(CCN(C)CCCc2nc3ccccc3[nH]2)CCc2cc(F)ccc2C1C(C)C.Cl.Cl |
| Storage condition | 2-8℃ |
Toxicological Information
CHEMICAL IDENTIFICATION |
ACUTE TOXICITY DATA - TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- >800 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 9,4,1991
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 23 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 9,4,1991
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- >800 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 9,4,1991
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 35 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- REFERENCE :
- CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 9,4,1991 ** REPRODUCTIVE DATA **
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 270 mg/kg
- SEX/DURATION :
- female 10-12 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
- REFERENCE :
- REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987- Volume(issue)/page/year: 11,207,1997
Safety Information
| WGK Germany | 3 |
|---|---|
| RTECS | AI8977250 |
Synonyms
| (1S,2S)-2-(2-{[3-(1H-Benzimidazol-2-yl)propyl](methyl)amino}ethyl)-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate dihydrochloride |
| (1S,2S)-2-(2-{[3-(1H-benzimidazol-2-yl)propyl](methyl)amino}ethyl)-6-fluoro-1-(propan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate dihydrochloride |
| [(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 |
| Mibefradil hydrochloride |
| (1s,2s)-(2-((3-(2-benzimidazolyl)propyl)methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl methoxyacetate dihydrochloride |
| (1S-cis)-Methoxyacetic Acid 2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl Ester Dihydrochloride |
| (1S,2S)-2-(2-{[3-(1H-Benzimidazol-2-yl)propyl](methyl)amino}ethyl)-6-fluoro-1-isopropyl-1,2,3,4-tetrahydro-2-naphthalenyl methoxyacetate dihydrochloride |
| Acetic acid, 2-methoxy-, (1S,2S)-2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl ester, hydrochloride (1:2) |
| Mibefradil (dihydrochloride) |
