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Details

Stereochemistry ACHIRAL
Molecular Formula C26H26F2N2.2ClH
Molecular Weight 477.417
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of FLUNARIZINE HYDROCHLORIDE

SMILES

Cl.Cl.FC1=CC=C(C=C1)C(N2CCN(C\C=C\C3=CC=CC=C3)CC2)C4=CC=C(F)C=C4

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 404.4948
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

CNS Active
3913
Curator's Comment: The drug quickly crosses the blood-brain barrier; concentrations in the brain are approximately 10 times higher than those in plasma.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
Antagonist
2778
 0.228 µM [IC50]
Blocker
537
Blocker
537
Antagonist
2778
 86.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Approved
8429
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
Approved
8429
FLURIZIN

Approved Use

Flurizin is indicated for treatment of peripheral vascular disease
Primary
Approved
8429
FLURIZIN

Approved Use

Flurizin is indicated for symptomatic treatment of vestibular vertigo (due to a diagnosed functional disorder of the vestibular system).
Primary
Approved
8429
FLURIZIN

Approved Use

Flurizin is indicated for treatment of motion sickness.
Palliative
Approved
8429
FLURIZIN

Approved Use

Flurizin is indicated for treatment of refractory epilepsy resistant to conventional antiepileptic therapy
Primary
Phase IV
63
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Aggravation of Parkinson's disease by cinnarizine.
1988 Jan
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
[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
Possible pharmacokinetic and pharmacodynamic factors affecting parkinsonism inducement by cinnarizine and flunarizine.
1995 Nov 9
Etiology of parkinsonism in a Brazilian movement disorders clinic.
1998 Jun
[Influence of co-administered antiepileptic drugs on nitrazepam tolerance in mice].
1998 Nov
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
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

Patents

JP2001519394A
2
JP2002520274A
21
JP2011513484A
29
JP4475802B2
5
JP4705912B2
47
JPH00597675A
7
JPH01238543A
5
JPH04368338A
11
JPH05271069A
4
JPH05294848A
2
JPH0597675A
2
JPH0761937A
11
JPH1135483A
4
JPS62270519A
2
JPS6322007A
2

Sample Use Guides

In Vivo Use Guide
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 Dec 15 15:23:27 UTC 2023
Edited
by admin
on Fri Dec 15 15:23:27 UTC 2023
Record UNII
C11102TO53
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLUNARIZINE HYDROCHLORIDE
JAN   MART.   USAN  
USAN  
Official 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 [WHO-DD]
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 Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL30008
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
EVMPD
SUB02213MIG
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
NCI_THESAURUS
C81684
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
PUBCHEM
5282407
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
ECHA (EC/EINECS)
250-216-6
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
SMS_ID
100000090416
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
EPA CompTox
DTXSID80184554
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
NSC
757807
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
DRUG BANK
DBSALT000382
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
RXCUI
82019
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY RxNorm
CAS
30484-77-6
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
FDA UNII
C11102TO53
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY
MERCK INDEX
m5445
Created by admin on Fri Dec 15 15:23:27 UTC 2023 , Edited by admin on Fri Dec 15 15:23:27 UTC 2023
PRIMARY Merck Index
Related Record Type Details
Structure of FLUNARIZINE
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of 1-[(4-Fluorophenyl)phenylmethyl]-4-(3-phenyl-2-propen-1-yl)piperazine
IMPURITY -> PARENT
Structure of Flunarizine, (Z)-
IMPURITY -> PARENT
Structure of 1-[(2-fluorophenyl)(4-fluorophenyl)methyl]-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine
IMPURITY -> PARENT
Structure of 1-(Bis(4-fluorophenyl)methyl)piperazine
IMPURITY -> PARENT
Related Record Type Details
Structure of FLUNARIZINE
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