Synonym
Flunarizine, Sibelium, Flunarizina, Flunarizinum, Flunarizin, R-14950
IUPAC/Chemical Name
1-[bis(4-fluorophenyl)methyl]-4-[(E)-3-phenylprop-2-enyl]piperazine
InChi Key
OFBIFZUFASYYRE-UHFFFAOYSA-N
InChi Code
InChI=1S/C15H14FN3O3/c1-3-22-15(21)13-12-7-18(2)14(20)10-6-9(16)4-5-11(10)19(12)8-17-13/h4-6,8H,3,7H2,1-2H3
SMILES Code
O=C(C1=C(CN2C)N(C=N1)C3=CC=C(F)C=C3C2=O)OCC
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Flunarizine is a potent dual Na+/Ca2+ channel (T-type) blocker.
In vitro activity:
Application of FLN (flunarizine) produced a significant cytotoxic effect on U-87 MG (Fig. 1A), LN-229 (Fig. 1B), and U-118 MG (Fig. 1C) cells. The results of cell survival and colony formation assay suggested that FLN exhibited anti-proliferation activity in GBM cells.
Reference: Eur J Pharmacol. 2021 Feb 5;892:173756. https://pubmed.ncbi.nlm.nih.gov/33245897/
In vivo activity:
The flunarizine treatment significantly extended lifespan of ≈40% with a shift in mean survival of SMA mice (16.3 versus 11.7 days; Mantel-Cox test, p = 0.0002).
Reference: Sci Rep. 2018; 8: 2075. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794986/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
303.29
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Kim HJ, Lee J, Lee GR, Kim N, Lee HI, Kwon M, Kim NY, Park JH, Kang YH, Song HJ, Kim T, Shin DM, Jeong W. Flunarizine inhibits osteoclastogenesis by regulating calcium signaling and promotes osteogenesis. J Cell Physiol. 2021 Jun 30. doi: 10.1002/jcp.30496. Epub ahead of print. PMID: 34192358.
2. Chen SH, Chao CN, Chen SY, Lin HP, Huang HY, Fang CY. Flunarizine, a drug approved for treating migraine and vertigo, exhibits cytotoxicity in GBM cells. Eur J Pharmacol. 2021 Feb 5;892:173756. doi: 10.1016/j.ejphar.2020.173756. Epub 2020 Nov 25. PMID: 33245897.
3. Sapaly D, Dos Santos M, Delers P, Biondi O, Quérol G, Houdebine L, Khoobarry K, Girardet F, Burlet P, Armand AS, Chanoine C, Bureau JF, Charbonnier F, Lefebvre S. Small-molecule flunarizine increases SMN protein in nuclear Cajal bodies and motor function in a mouse model of spinal muscular atrophy. Sci Rep. 2018 Feb 1;8(1):2075. doi: 10.1038/s41598-018-20219-1. PMID: 29391529; PMCID: PMC5794986.
In vitro protocol:
1. Kim HJ, Lee J, Lee GR, Kim N, Lee HI, Kwon M, Kim NY, Park JH, Kang YH, Song HJ, Kim T, Shin DM, Jeong W. Flunarizine inhibits osteoclastogenesis by regulating calcium signaling and promotes osteogenesis. J Cell Physiol. 2021 Jun 30. doi: 10.1002/jcp.30496. Epub ahead of print. PMID: 34192358.
2. Chen SH, Chao CN, Chen SY, Lin HP, Huang HY, Fang CY. Flunarizine, a drug approved for treating migraine and vertigo, exhibits cytotoxicity in GBM cells. Eur J Pharmacol. 2021 Feb 5;892:173756. doi: 10.1016/j.ejphar.2020.173756. Epub 2020 Nov 25. PMID: 33245897.
In vivo protocol:
1. Kim HJ, Lee J, Lee GR, Kim N, Lee HI, Kwon M, Kim NY, Park JH, Kang YH, Song HJ, Kim T, Shin DM, Jeong W. Flunarizine inhibits osteoclastogenesis by regulating calcium signaling and promotes osteogenesis. J Cell Physiol. 2021 Jun 30. doi: 10.1002/jcp.30496. Epub ahead of print. PMID: 34192358.
2. Sapaly D, Dos Santos M, Delers P, Biondi O, Quérol G, Houdebine L, Khoobarry K, Girardet F, Burlet P, Armand AS, Chanoine C, Bureau JF, Charbonnier F, Lefebvre S. Small-molecule flunarizine increases SMN protein in nuclear Cajal bodies and motor function in a mouse model of spinal muscular atrophy. Sci Rep. 2018 Feb 1;8(1):2075. doi: 10.1038/s41598-018-20219-1. PMID: 29391529; PMCID: PMC5794986.
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8: McLean MJ. In vitro electrophysiological evidence predicting anticonvulsant efficacy of memantine and flunarizine. Pol J Pharmacol Pharm. 1987 Sep-Oct;39(5):513-25. Review. PubMed PMID: 3333611.
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10: Wouters L, Amery W, Towse G. Flunarizine in the treatment of vertigo. J Laryngol Otol. 1983 Aug;97(8):697-704. Review. PubMed PMID: 6350513.
11: Amery WK. Flunarizine, a calcium channel blocker: a new prophylactic drug in migraine. Headache. 1983 Mar;23(2):70-4. Review. PubMed PMID: 6343298.
12: Teive HA, Troiano AR, Germiniani FM, Werneck LC. Flunarizine and cinnarizine-induced parkinsonism: a historical and clinical analysis. Parkinsonism Relat Disord. 2004 Jun;10(4):243-5. Review. PubMed PMID: 15120099.
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14: Schmidt R, Oestreich W. Flunarizine in migraine prophylaxis: the clinical experience. J Cardiovasc Pharmacol. 1991;18 Suppl 8:S21-6. Review. PubMed PMID: 1726732.
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16: Lastra Martínez L, Herranz Fernández J, Arteaga Manjón-Cabez R. [Flunarizine and dihydroergotamine in the treatment of migraine in children]. An Esp Pediatr. 1990 Mar;32(3):213-8. Review. Spanish. Erratum in: An Esp Pediatr 1990 Jun;32(6):566. PubMed PMID: 2189328.
17: Todd PA, Benfield P. Flunarizine. A reappraisal of its pharmacological properties and therapeutic use in neurological disorders. Drugs. 1989 Oct;38(4):481-99. Review. PubMed PMID: 2684591.
18: Bakchine S, Lacomblez L, Soubrié C. [Extrapyramidal syndrome during treatment with flunarizine]. Rev Neurol (Paris). 1988;144(12):833-4. Review. French. PubMed PMID: 3070697.
19: Kurihara J, Kato H. [Agents to improve cerebrovascular circulation and cerebral metabolism--flunarizine]. Nihon Rinsho. 1985 Feb;43(2):402-5. Review. Japanese. PubMed PMID: 3889415.
20: Holmes B, Brogden RN, Heel RC, Speight TM, Avery GS. Flunarizine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs. 1984 Jan;27(1):6-44. Review. PubMed PMID: 6141044.
