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Details

Stereochemistry ACHIRAL
Molecular Formula C26H26F2N2.2ClH
Molecular Weight 477.4176
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of FLUNARIZINE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=RXKMOPXNWTYEHI-RDRKJGRWSA-N
InChI=1S/C26H26F2N2.2ClH/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;2*1H/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

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
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
Anticonvulsive properties of cinnarizine and flunarizine in rats and mice.
1975 Sep
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
Ca2+ modulators as antidotes to imipramine and neurotransmitter toxicity.
1987 Sep
Movement disorders and depression due to flunarizine and cinnarizine.
1989
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
Selective dysfunction of the vagal component of the baroreflex following cerebral ischemia: protection by ifenprodil and flunarizine.
1990 Nov 6
Comparison of the efficacy and safety of flunarizine to propranolol in the prophylaxis of migraine.
1992 Aug
[A case report of severe urinary retention and meteorism during flunarizine administration].
1992 Mar
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
Evidence of sex related differences in the effects of calcium channel blockers on neuroleptic-induced catalepsy in mice.
1999 Feb
Distinct features of seizures induced by cocaine and amphetamine analogs.
1999 Jul 21
Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers.
2000 Feb
Parkinsonism and other movement disorders in outpatients in chronic use of cinnarizine and flunarizine.
2004 Sep
Atypical antipsychotic profile of flunarizine in animal models.
2005 Jan
Amphetamine-induced anxiety-related behavior in animal models.
2007 Nov-Dec
Treatment of migraine with prophylactic drugs.
2008 Oct
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
Ameliorative effect of flunarizine in cisplatin-induced acute renal failure via mitochondrial permeability transition pore inactivation in rats.
2011 Jan
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 21:12:57 UTC 2021
Edited
by admin
on Fri Jun 25 21:12:57 UTC 2021
Record UNII
C11102TO53
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLUNARIZINE HYDROCHLORIDE
JAN   MART.   USAN  
USAN  
Official Name English
FLUNARIZINE DIHYDROCHLORIDE [WHO-DD]
Common Name English
FLUNARIZINE HCL
Common Name English
R-14950
Code English
(E)-1-(BIS-(P-FLUOROPHENYL)METHYL)-4-CINNAMYLPIPERAZINE DIHYDROCHLORIDE
Common Name English
PIPERAZINE, 1-(BIS(4-FLUOROPHENYL)METHYL)-4-(3-PHENYL-2-PROPENYL)-, DIHYDROCHLORIDE, (E)-
Common Name English
R 14,950
Code English
FLUNARIZINE DIHYDROCHLORIDE [MI]
Common Name English
FLUNARIZINE (AS HYDROCHLORIDE)
Common Name English
FLUNARIZINE DIHYDROCHLORIDE [EP MONOGRAPH]
Common Name English
FLUNARIZINE HYDROCHLORIDE [USAN]
Common Name English
FLUNARIZINE HYDROCHLORIDE [JAN]
Common Name English
FLUNARIZINE DIHYDROCHLORIDE
EP   MI   WHO-DD  
Common Name English
NSC-757807
Code English
FLUNARIZINE HYDROCHLORIDE [MART.]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C333
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL30008
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY
EVMPD
SUB02213MIG
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY
NCI_THESAURUS
C81684
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY
PUBCHEM
5282407
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY
ECHA (EC/EINECS)
250-216-6
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY
EPA CompTox
30484-77-6
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY
DRUG BANK
DBSALT000382
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY
RXCUI
82019
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY RxNorm
CAS
30484-77-6
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY
FDA UNII
C11102TO53
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY
MERCK INDEX
M5445
Created by admin on Fri Jun 25 21:12:57 UTC 2021 , Edited by admin on Fri Jun 25 21:12:57 UTC 2021
PRIMARY Merck Index
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ACTIVE MOIETY