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Details

Stereochemistry ACHIRAL
Molecular Formula C26H26F2N2
Molecular Weight 404.4958
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of FLUNARIZINE

SMILES

c1ccc(cc1)/C(/[H])=C(\[H])/CN2CCN(CC2)C(c3ccc(cc3)F)c4ccc(cc4)F

InChI

InChIKey=SMANXXCATUTDDT-QPJJXVBHSA-N
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+

HIDE SMILES / InChI

Molecular Formula C26H26F2N2
Molecular Weight 404.4958
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 / dopamine D2 blocking activity. It is not available in the US but marketed in other countries for prophylaxis of a migraine, occlusive peripheral vascular disease, the vertigo of central and peripheral origin, motion sickness and as an adjuvant in the therapy of epilepsy. The drug is also investigated for the treatment of schizophrenia.

CNS Activity

Curator's Comment:: The drug quickly crosses the blood-brain barrier; concentrations in the brain are approximately 10 times higher than those in plasma.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
SIBELIUM

Approved Use

In the prophylaxis of a migraine. The limited information available for periods longer than 12 months has shown flunarizine to continue to be effective. Patients should be regularly reviewed to assess their response to treatment, and if a sustained attack-free period is established, interrupted flunarizine treatment should be considered.

Launch Date

1.23318724E12
Primary
FLURIZIN

Approved Use

Flurizin is indicated for treatment of peripheral vascular disease
Primary
FLURIZIN

Approved Use

Flurizin is indicated for symptomatic treatment of vestibular vertigo (due to a diagnosed functional disorder of the vestibular system).
Primary
FLURIZIN

Approved Use

Flurizin is indicated for treatment of motion sickness.
Palliative
FLURIZIN

Approved Use

Flurizin is indicated for treatment of refractory epilepsy resistant to conventional antiepileptic therapy
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Flunarizine in common migraine: Italian cooperative trial. II. Long-term follow-up.
1985 May
Parkinsonism, tardive dyskinesia, akathisia, and depression induced by flunarizine.
1986 Aug 2
Parkinsonism, tardive dyskinesia, akathisia, and depression induced by flunarizine.
1986 Jun 7
Non-vascular action of calcium blockers in migraine: pupillopharmacological study.
1986 Oct-Dec
Flunarizine- and cinnarizine-induced extrapyramidal reactions.
1987 May
Ca2+ modulators as antidotes to imipramine and neurotransmitter toxicity.
1987 Sep
Aggravation of Parkinson's disease by cinnarizine.
1988 Jan
Cardiovascular and renal actions of calcium channel blocker chemical subgroups: a search for renal specificity.
1988 Jun
Parkinsonism, tremor, and depression induced by cinnarizine and flunarizine.
1988 Sep 17
Movement disorders and depression due to flunarizine and cinnarizine.
1989
Calcium channel inhibitors prevent apomorphine- and oxytocin-induced penile erection and yawning in male rats.
1989 Aug 3
Drug-induced tremor of the tongue.
1989 Feb
Extrapyramidal and depressive side reactions with flunarizine and cinarizine.
1989 Feb
Effect of flunarizine on the attenuation of baroreflex by transient cerebral ischemia.
1989 Jun 8
Termination of ouabain-induced ventricular tachycardia by flunarizine in conscious dogs.
1989 Jun 8
[Protective effect of calcium channel blockers on the liver against halothane hepatitis in rats].
1990 Feb
Oxytocin-induced penile erection and yawning: role of calcium and prostaglandins.
1990 Mar
Selective dysfunction of the vagal component of the baroreflex following cerebral ischemia: protection by ifenprodil and flunarizine.
1990 Nov 6
Investigation of anti-motion sickness drugs in the squirrel monkey.
1992 Feb
Calcium-entry blockers-induced parkinsonism: possible role of inherited susceptibility.
1992 Spring
Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema.
1993 Dec
Effect of calcium channel antagonists on cocaine-induced malignant arrhythmias: protection against ventricular fibrillation.
1993 Jul
Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S-312-d. 5th communication: anticonvulsant effects in mice.
1994 Jun
The effect of flunarizine and ryanodine on acquired torsades de pointes arrhythmias in the intact canine heart.
1995 Mar
Possible pharmacokinetic and pharmacodynamic factors affecting parkinsonism inducement by cinnarizine and flunarizine.
1995 Nov 9
Postmarketing study of the use of flunarizine in vestibular vertigo and in migraine.
1996
Catalepsy induced by manidipine, a calcium channel blocker, in mice.
1996 Apr
Post-marketing cohort study comparing the safety and efficacy of flunarizine and propranolol in the prophylaxis of migraine.
1996 Aug
A long-term follow-up study of cinnarizine- and flunarizine-induced parkinsonism.
1997 Jan
Etiology of parkinsonism in a Brazilian movement disorders clinic.
1998 Jun
Catalepsy induced by calcium channel blockers in mice.
1998 Mar
[Influence of co-administered antiepileptic drugs on nitrazepam tolerance in mice].
1998 Nov
Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers.
2000 Feb
Atypical antipsychotic profile of flunarizine in animal models.
2005 Jan
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces calcium influx through T-type calcium channel and enhances lysosomal exocytosis and insulin secretion in INS-1 cells.
2009 May-Jun
Progressive supranuclear palsy-like syndrome induced by amiodarone and flunarizine.
2009 Sep
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle.
2010 Feb 23
The differential diagnoses of parkinsonism: findings from a cohort of 1528 patients and a 10 years comparison in tertiary movement disorders clinics.
2010 Jun
Ameliorative effect of flunarizine in cisplatin-induced acute renal failure via mitochondrial permeability transition pore inactivation in rats.
2011 Jan
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.
2013 Sep 5
Patents

Sample Use Guides

Oral; the recommended dose is 10mg/day at bedtime.
Route of Administration: Oral
In Vitro Use Guide
To study the effect of flunarizine on the interaction between calmodulin and phosphodiesterase, proteins were isolated from bovine brain. PDE activity was measured using cAMP (1.2mM) as a substrate and in the presence of 5'-nucleotidase. The liberated Pi was measured in the supernatant by the method of Ames. The reaction was performed in the presence of CaCl2 and Calmodulin (positive control), in the presence of EGTA (negative control) and in the presence of various concentrations of flunarizine. IC50 determined for brain PDE was 21 uM.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:29:56 UTC 2021
Edited
by admin
on Fri Jun 25 21:29:56 UTC 2021
Record UNII
R7PLA2DM0J
Record Status Validated (UNII)
Record Version
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Name Type Language
FLUNARIZINE
INN   MI   WHO-DD  
INN  
Official Name English
PIPERAZINE, 1-(BIS(4-FLUOROPHENYL)METHYL)-4-(3-PHENYL-2-PROPENYL)-, (E)-
Common Name English
FLUNARIZINE [INN]
Common Name English
(E)-1-(BIS-(P-FLUOROPHENYL)METHYL)-4-CINNAMYLPIPERAZINE
Common Name English
FLUNARIZINE [WHO-DD]
Common Name English
FLUNARIZINE [MI]
Common Name English
SIBELIUM
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C29578
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
NCI_THESAURUS C333
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
FDA ORPHAN DRUG 528116
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
WHO-ATC N07CA03
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
FDA ORPHAN DRUG 823521
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
WHO-VATC QN07CA03
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
FDA ORPHAN DRUG 9485
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
FDA ORPHAN DRUG 398513
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
FDA ORPHAN DRUG 665818
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
Code System Code Type Description
ECHA (EC/EINECS)
257-937-5
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
NCI_THESAURUS
C83718
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
ChEMBL
CHEMBL30008
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
EPA CompTox
52468-60-7
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
MESH
D005444
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
DRUG CENTRAL
1200
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
DRUG BANK
DB04841
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
INN
2686
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PRIMARY
RXCUI
4459
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
FLUNARIZINE
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
CAS
52468-60-7
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
LACTMED
Flunarizine
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
PUBCHEM
941361
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
EVMPD
SUB07707MIG
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
FDA UNII
R7PLA2DM0J
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY
MERCK INDEX
M5445
Created by admin on Fri Jun 25 21:29:56 UTC 2021 , Edited by admin on Fri Jun 25 21:29:56 UTC 2021
PRIMARY Merck Index
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ACTIVE MOIETY