FLUNARIZINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H26F2N2
Molecular Weight	404.4948
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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	404.4948
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.nice.org.uk/advice/esuom33/chapter/Key-points-from-the-evidence

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Calmodulin 17 Target ID: CHEMBL6093 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6093793	Inhibitor 8297
Dopamine D2 receptor 297 Target ID: CHEMBL339 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10571163	Antagonist 2778	0.228 µM [IC50]
Voltage-gated T-type calcium channel 17 Target ID: CHEMBL2362995 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10571163	Blocker 537
Sodium channel alpha subunits; brain (Types I, II, III) 28 Target ID: CHEMBL2096682 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10571163	Blocker 537
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20493137	Antagonist 2778	86.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Migraine 103 Sources: http://www.medicines.ie/medicine/14498/SPC/Sibelium+5+mg+tablets/#INDICATIONS	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 2009
Occlusive peripheral vascular disease 2 Sources: https://www.squarepharma.com.bd/downloads/Flurizin.pdf	Primary	Approved 8429	FLURIZIN Approved Use Flurizin is indicated for treatment of peripheral vascular disease
Vestibular vertigo 2 Sources: https://www.squarepharma.com.bd/downloads/Flurizin.pdf	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).
Motion sickness 43 Sources: https://www.squarepharma.com.bd/downloads/Flurizin.pdf	Primary	Approved 8429	FLURIZIN Approved Use Flurizin is indicated for treatment of motion sickness.
Epilepsy 121 Sources: https://www.squarepharma.com.bd/downloads/Flurizin.pdf	Palliative	Approved 8429	FLURIZIN Approved Use Flurizin is indicated for treatment of refractory epilepsy resistant to conventional antiepileptic therapy
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19192440	Primary	Phase IV 63	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Flunarizine in common migraine: Italian cooperative trial. II. Long-term follow-up.	1985 May	3893736
Flunarizine- and cinnarizine-induced extrapyramidal reactions.	1987 May	3574697
Ca2+ modulators as antidotes to imipramine and neurotransmitter toxicity.	1987 Sep	2886994
Aggravation of Parkinson's disease by cinnarizine.	1988 Jan	3351524
Parkinsonism, tremor, and depression induced by cinnarizine and flunarizine.	1988 Sep 17	3147743
Effect of flunarizine on the attenuation of baroreflex by transient cerebral ischemia.	1989 Jun 8	2767131
Termination of ouabain-induced ventricular tachycardia by flunarizine in conscious dogs.	1989 Jun 8	2767130
[Protective effect of calcium channel blockers on the liver against halothane hepatitis in rats].	1990 Feb	2325253
Oxytocin-induced penile erection and yawning: role of calcium and prostaglandins.	1990 Mar	2339153
Calcium-entry blockers-induced parkinsonism: possible role of inherited susceptibility.	1992 Spring	1508427
Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S-312-d. 5th communication: anticonvulsant effects in mice.	1994 Jun	7967231
The effect of flunarizine and ryanodine on acquired torsades de pointes arrhythmias in the intact canine heart.	1995 Mar	7620644
Possible pharmacokinetic and pharmacodynamic factors affecting parkinsonism inducement by cinnarizine and flunarizine.	1995 Nov 9	7503767
Post-marketing cohort study comparing the safety and efficacy of flunarizine and propranolol in the prophylaxis of migraine.	1996 Aug	8869768
A long-term follow-up study of cinnarizine- and flunarizine-induced parkinsonism.	1997 Jan	8990063
Etiology of parkinsonism in a Brazilian movement disorders clinic.	1998 Jun	9698723
Catalepsy induced by calcium channel blockers in mice.	1998 Mar	9533112
[Influence of co-administered antiepileptic drugs on nitrazepam tolerance in mice].	1998 Nov	9844417
Evidence of sex related differences in the effects of calcium channel blockers on neuroleptic-induced catalepsy in mice.	1999 Feb	10368871
Atypical antipsychotic profile of flunarizine in animal models.	2005 Jan	15290004
The differential diagnoses of parkinsonism: findings from a cohort of 1528 patients and a 10 years comparison in tertiary movement disorders clinics.	2010 Jun	20347518
Ameliorative effect of flunarizine in cisplatin-induced acute renal failure via mitochondrial permeability transition pore inactivation in rats.	2011 Jan	21058009
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.	2013 Sep 5	23769903

Patents

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 16:16:46 GMT 2023` Edited by `admin` on `Fri Dec 15 16:16:46 GMT 2023`
Record UNII	R7PLA2DM0J
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

FLUNARIZINE

Official Name

English

PIPERAZINE, 1-(BIS(4-FLUOROPHENYL)METHYL)-4-(3-PHENYL-2-PROPENYL)-, (E)-

Common Name

English

Flunarizine [WHO-DD]

Common Name

English

flunarizine [INN]

Common Name

English

(E)-1-(BIS-(P-FLUOROPHENYL)METHYL)-4-CINNAMYLPIPERAZINE

Common Name

English

FLUNARIZINE [MI]

Common Name

English

SIBELIUM

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578