Details of the Drug

General Information of Drug (ID: DMZU5JP)

Drug Name
Flunarizine
Synonyms
Flufenal; Flunarizin; Flunarizina; Flunarizinum; Fluvert; Issium; Sibelium; Vertix; Zinasen; Apo-flunarizine capsules; Flunarizina [INN-Spanish]; Flunarizine (INN); Flunarizine [INN:BAN]; Flunarizinum [INN-Latin]; Novo-Flunarizine; R-14950; Sibelium (TN); (E)-1-(Bis(4-fluorophenyl)methyl)-4-(3-phenyl-2-propenyl)piperazine; (E)-1-[Bis-(p-fluorophenyl)methyl]-4-cinnamylpiperazine; 1-(Bis(4-fluorophenyl)methyl)-4-cinnamylpiperazine; 1-[bis(4-fluorophenyl)methyl]-4-(3-phenylprop-2-en-1-yl)piperazine; 1-[bis(4-fluorophenyl)methyl]-4-[(E)-3-phenylprop-2-enyl]piperazine
Indication
Disease Entry ICD 11 Status REF
Migraine 8A80 Approved [1]
Therapeutic Class
Anticonvulsants
Affected Organisms
Humans and other mammals
ATC Code
N07CA03: Flunarizine
N07CA: Antivertigo preparations
N07C: ANTIVERTIGO PREPARATIONS
N07: OTHER NERVOUS SYSTEM DRUGS
N: NERVOUS SYSTEM
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 404.5
Logarithm of the Partition Coefficient (xlogp) 6
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
Absorption
The oral absorption of drug is 85% []
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Elimination
0.2% of drug is excreted from urine in the unchanged form [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 18 days [3]
Metabolism
The drug is metabolized via the hepatic []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.3532 micromolar/kg/day [4]
Water Solubility
The ability of drug to dissolve in water is measured as 0.0165 mg/mL [2]
Chemical Identifiers
Formula
C26H26F2N2
IUPAC Name
1-[bis(4-fluorophenyl)methyl]-4-[(E)-3-phenylprop-2-enyl]piperazine
Canonical 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+
InChIKey
SMANXXCATUTDDT-QPJJXVBHSA-N
Cross-matching ID
PubChem CID
941361
ChEBI ID
CHEBI:92209
CAS Number
52468-60-7
UNII
R7PLA2DM0J
DrugBank ID
DB04841
TTD ID
D05CEU
VARIDT ID
DR00727
INTEDE ID
DR0708
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Voltage-gated calcium channel alpha Cav2.1 (CACNA1A) TTX4QDJ CAC1A_HUMAN Inhibitor [5]
Voltage-gated calcium channel alpha Cav3.2 (CACNA1H) TTZPWGN CAC1H_HUMAN Blocker [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [7]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [8]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Substrate [8]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Substrate [8]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Migraine
ICD Disease Classification 8A80
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Voltage-gated calcium channel alpha Cav3.2 (CACNA1H) DTT CACNA1H 1.31E-04 -0.76 -2.12
Cytochrome P450 2A6 (CYP2A6) DME CYP2A6 5.94E-01 -9.00E-02 -4.71E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 1.57E-01 -2.01E-01 -6.73E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 1.02E-01 -3.26E-02 -1.33E-01
Cytochrome P450 1A1 (CYP1A1) DME CYP1A1 5.71E-01 -1.43E-01 -5.46E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 2.69E-01 6.97E-02 1.48E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 012102.
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
6 Positive allosteric interaction of structurally diverse T-type calcium channel antagonists. Cell Biochem Biophys. 2009;55(2):81-93.
7 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
8 Oxidative metabolism of flunarizine and cinnarizine by microsomes from B-lymphoblastoid cell lines expressing human cytochrome P450 enzymes. Biol Pharm Bull. 1996 Nov;19(11):1511-4.