flunarizine   Click here for help

GtoPdb Ligand ID: 12488

Synonyms: R-14950 | R14950 | Sibelium®
Approved drug
flunarizine is an approved drug
Compound class: Synthetic organic
Comment: Flunarizine has been demonstrated to exhibit multiple activities [4]: calcium entry blocker [2,6] with calmodulin binding properties, histamine H1 receptor antagonism, dopamine D2 receptor antagonism. It is a fluorine derivative of cinnarizine. Both of these compounds induce parkinsonism as an adverse effect [3,9], likely due to antagonism of D2 receptors by the parent molecules and/or some of their bioactive metabolites [5].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 0
Rotatable bonds 6
Topological polar surface area 6.48
Molecular weight 404.5
XLogP 3.01
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C1=CC=C(C=C1)/C=C/CN2CCN(CC2)C(C3=CC=C(C=C3)F)C4=CC=C(C=C4)F
Isomeric SMILES C1CN(CCN1C/C=C/C2=CC=CC=C2)C(C3=CC=C(C=C3)F)C4=CC=C(C=C4)F
InChI InChI=1S/C26H26F2N2/c27-24-12-8-22(9-13-24)26(23-10-14-25(28)15-11-23)30-19-17-29(18-20-30)16-4-7-21-5-2-1-3-6-21/h1-15,26H,16-20H2/b7-4+
InChI Key SMANXXCATUTDDT-QPJJXVBHSA-N
References
1. Ambrosio C, Stefanini E. (1991)
Interaction of flunarizine with dopamine D2 and D1 receptors.
Eur J Pharmacol, 197 (2-3): 221-3. [PMID:1833208]
2. Amery WK. (1983)
Flunarizine, a calcium channel blocker: a new prophylactic drug in migraine.
Headache, 23 (2): 70-4. [PMID:6343298]
3. Capellà D, Laporte JR, Castel JM, Tristán C, Cos A, Morales-Olivas FJ. (1988)
Parkinsonism, tremor, and depression induced by cinnarizine and flunarizine.
BMJ, 297 (6650): 722-3. [PMID:3147743]
4. Holmes B, Brogden RN, Heel RC, Speight TM, Avery GS. (1984)
Flunarizine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use.
Drugs, 27 (1): 6-44. [PMID:6141044]
5. Kariya S, Isozaki S, Masubuchi Y, Suzuki T, Narimatsu S. (1995)
Possible pharmacokinetic and pharmacodynamic factors affecting parkinsonism inducement by cinnarizine and flunarizine.
Biochem Pharmacol, 50 (10): 1645-50. [PMID:7503767]
6. Olesen J. (1986)
Role of calcium entry blockers in the prophylaxis of migraine.
Eur Neurol, 25 Suppl 1: 72-9. [PMID:3530775]
7. Santi CM, Cayabyab FS, Sutton KG, McRory JE, Mezeyova J, Hamming KS, Parker D, Stea A, Snutch TP. (2002)
Differential inhibition of T-type calcium channels by neuroleptics.
J Neurosci, 22 (2): 396-403. [PMID:11784784]
8. Shen Y, Qi X, Wan T. (2020)
The Treatment of Vestibular Migraine: A Narrative Review.
Ann Indian Acad Neurol, 23 (5): 602-607. [PMID:33623258]
9. Teive HA, Troiano AR, Germiniani FM, Werneck LC. (2004)
Flunarizine and cinnarizine-induced parkinsonism: a historical and clinical analysis.
Parkinsonism Relat Disord, 10 (4): 243-5. [PMID:15120099]
10. von Brevern M, Lempert T. (2020)
Vestibular Migraine: Treatment and Prognosis.
Semin Neurol, 40 (1): 83-86. [PMID:31887753]