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)

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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: CHEMBL30008
CAS Number: 52468-60-7
UNII: R7PLA2DM0J
DrugBank ID: DB04841
TTD ID: D05CEU
VARIDT ID: DR00727
INTEDE ID: DR0708

Drug-Molecule Activity Atlas (DMA)^NEW

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Drug Pharmacogenomic Perturbation (DPP)^NEW

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Drug ADMET Endpoint Profile (DAE)^NEW

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Combinatorial Drugs (CBD)

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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)

MIA Detail

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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)

MEA Detail

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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.