FLUNARIZINE

Possibly Marketed Outside US

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 8504
Dopamine D2 receptor 311 Target ID: CHEMBL339 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10571163	Antagonist 2849	0.228 µM [IC50]
Voltage-gated T-type calcium channel 19 Target ID: CHEMBL2362995 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10571163	Blocker 555
Sodium channel alpha subunits; brain (Types I, II, III) 28 Target ID: CHEMBL2096682 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10571163	Blocker 555
Histamine H1 receptor 316 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20493137	Antagonist 2849	86.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Migraine 107 Sources: http://www.medicines.ie/medicine/14498/SPC/Sibelium+5+mg+tablets/#INDICATIONS	Preventing	Approved 8583	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 8583	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 8583	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 8583	FLURIZIN Approved Use Flurizin is indicated for treatment of motion sickness.
Epilepsy 121 Sources: https://www.squarepharma.com.bd/downloads/Flurizin.pdf	Palliative	Approved 8583	FLURIZIN Approved Use Flurizin is indicated for treatment of refractory epilepsy resistant to conventional antiepileptic therapy
Schizophrenia 305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19192440	Primary	Phase IV 63	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
20.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34472200/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUNARIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
35.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34472200/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUNARIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

AUC

Value	Dose	Co-administered	Analyte	Population
222.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34472200/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUNARIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
318 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34472200/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUNARIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

T_1/2

Value	Dose	Co-administered	Analyte	Population
30.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34472200/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUNARIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
26.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/34472200/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUNARIZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT

Doses

Dose	Population	Adverse events
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3893736/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3893736/	Disc. AE: Drowsiness, Weight gain... AEs leading to discontinuation/dose reduction: Drowsiness (4.2%) Weight gain (2.5%) Depression (5%) Sources: https://pubmed.ncbi.nlm.nih.gov/3893736/
5 mg 2 times / day multiple, oral Recommended Dose: 5 mg, 2 times / day Route: oral Route: multiple Dose: 5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27306581/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27306581/	Sources: https://pubmed.ncbi.nlm.nih.gov/27306581/
20 mg single, intravenous Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3180201/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3180201/	Other AEs: Somnolence, Nausea... Other AEs: Somnolence (25%) Nausea (5.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/3180201/
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3052850/	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3052850/	Disc. AE: Weight gain, Drowsiness... AEs leading to discontinuation/dose reduction: Weight gain Drowsiness Sources: https://pubmed.ncbi.nlm.nih.gov/3052850/

AEs

AE	Significance	Dose	Population
Weight gain	2.5% Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3893736/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3893736/
Drowsiness	4.2% Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3893736/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3893736/
Depression	5% Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3893736/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3893736/
Somnolence	25%	20 mg single, intravenous Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3180201/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3180201/
Nausea	5.6%	20 mg single, intravenous Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3180201/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3180201/
Drowsiness	Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3052850/	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3052850/
Weight gain	Disc. AE	10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3052850/	unhealthy, CHILD\|ADOLESCENT\|ADULT Health Status: unhealthy Age Group: CHILD\|ADOLESCENT\|ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3052850/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946	inhibitor 2438 substrate 1193	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 1079 CYP2C19 2057 CYP2E1 1060 OATP1B3 961 CYP2A6 879 BSEP 550 CYP1A2 2153 P-gp 1741 CYP2J2 33 CYP19A1 429	CYP2B6 776 CYP1A2 1197 CYP1A1 389 CYP2E1 729 CYP2C19 1119 CYP2A6 626 CYP2C8 810

Drug as perpetrator

Target	Modality	Activity
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/941361#section=BioAssay-Results Page: 280.0	inconclusive [IC50 21.1317 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDMwMDA4In19	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDMwMDA4In19	no [IC50 >10 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDMwMDA4In19	no [IC50 >50 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDMwMDA4In19	no [IC50 >50 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDMwMDA4In19	no [IC50 >50 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMzAwMDgifX0=	no [IC50 >50 uM]
CYP2J2 36	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/941361#section=BioAssay-Results Page: 4.0	yes [IC50 0.1 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMzAwMDgifX0=	yes [IC50 7.89 uM]
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDMwMDA4In19	yes [IC50 <10 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDU1MjY1OSJ9fQ==	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDU1MjY1OSJ9fQ==	yes [Inhibition 10 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/7924890/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8951176/	no
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8951176/	no
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8951176/	no
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8951176/	no
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8951176/	no
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8951176/	no
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8951176/	yes [Km 3.59 uM]
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8951176/	yes
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8951176/	yes
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/8951176/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMzAwMDgifX0=

PubMed

Title	Date	PubMed
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.	2013-09-05	23769903
Ameliorative effect of flunarizine in cisplatin-induced acute renal failure via mitochondrial permeability transition pore inactivation in rats.	2011-01	21058009
The differential diagnoses of parkinsonism: findings from a cohort of 1528 patients and a 10 years comparison in tertiary movement disorders clinics.	2010-06	20347518
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle.	2010-02-23	20142494
Progressive supranuclear palsy-like syndrome induced by amiodarone and flunarizine.	2009-09	19838530
EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force.	2009-09	19708964
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.	2009-06-24	19546254
Treatment of migraine with prophylactic drugs.	2008-10	18803445
Amphetamine-induced anxiety-related behavior in animal models.	2007-06-28	18195452
Atypical antipsychotic profile of flunarizine in animal models.	2005-01	15290004
Parkinsonism and other movement disorders in outpatients in chronic use of cinnarizine and flunarizine.	2004-09	15476069
Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers.	2000-02	11218825
Distinct features of seizures induced by cocaine and amphetamine analogs.	1999-07-21	10456426
Evidence of sex related differences in the effects of calcium channel blockers on neuroleptic-induced catalepsy in mice.	1999-02	10368871
[Influence of co-administered antiepileptic drugs on nitrazepam tolerance in mice].	1998-11	9844417
Etiology of parkinsonism in a Brazilian movement disorders clinic.	1998-06	9698723
Catalepsy induced by calcium channel blockers in mice.	1998-03	9533112
A long-term follow-up study of cinnarizine- and flunarizine-induced parkinsonism.	1997-01	8990063
Post-marketing cohort study comparing the safety and efficacy of flunarizine and propranolol in the prophylaxis of migraine.	1996-08	8869768
Catalepsy induced by manidipine, a calcium channel blocker, in mice.	1996-04	8794996
Postmarketing study of the use of flunarizine in vestibular vertigo and in migraine.	1996	8880046
Possible pharmacokinetic and pharmacodynamic factors affecting parkinsonism inducement by cinnarizine and flunarizine.	1995-11-09	7503767
The effect of flunarizine and ryanodine on acquired torsades de pointes arrhythmias in the intact canine heart.	1995-03	7620644
Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S-312-d. 5th communication: anticonvulsant effects in mice.	1994-06	7967231
Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema.	1993-12	7508328
Effect of calcium channel antagonists on cocaine-induced malignant arrhythmias: protection against ventricular fibrillation.	1993-07	8331569
Comparison of the efficacy and safety of flunarizine to propranolol in the prophylaxis of migraine.	1992-08	1393843
[A case report of severe urinary retention and meteorism during flunarizine administration].	1992-03	1593790
Investigation of anti-motion sickness drugs in the squirrel monkey.	1992-02	1613127
Calcium-entry blockers-induced parkinsonism: possible role of inherited susceptibility.	1992	1508427
Selective dysfunction of the vagal component of the baroreflex following cerebral ischemia: protection by ifenprodil and flunarizine.	1990-11-06	2076755
Oxytocin-induced penile erection and yawning: role of calcium and prostaglandins.	1990-03	2339153
[Protective effect of calcium channel blockers on the liver against halothane hepatitis in rats].	1990-02	2325253
Calcium channel inhibitors prevent apomorphine- and oxytocin-induced penile erection and yawning in male rats.	1989-08-03	2806374
Effect of flunarizine on the attenuation of baroreflex by transient cerebral ischemia.	1989-06-08	2767131
Termination of ouabain-induced ventricular tachycardia by flunarizine in conscious dogs.	1989-06-08	2767130
Drug-induced tremor of the tongue.	1989-02	2925349
Extrapyramidal and depressive side reactions with flunarizine and cinarizine.	1989-02	2703850
Movement disorders and depression due to flunarizine and cinnarizine.	1989	2733706
Parkinsonism, tremor, and depression induced by cinnarizine and flunarizine.	1988-09-17	3147743
Cardiovascular and renal actions of calcium channel blocker chemical subgroups: a search for renal specificity.	1988-06	2901472
Aggravation of Parkinson's disease by cinnarizine.	1988-01	3351524
Ca2+ modulators as antidotes to imipramine and neurotransmitter toxicity.	1987-09	2886994
Flunarizine- and cinnarizine-induced extrapyramidal reactions.	1987-05	3574697
Non-vascular action of calcium blockers in migraine: pupillopharmacological study.	1986-10-01	3038706
Parkinsonism, tardive dyskinesia, akathisia, and depression induced by flunarizine.	1986-08-02	2874317
Parkinsonism, tardive dyskinesia, akathisia, and depression induced by flunarizine.	1986-06-07	2872433
Flunarizine in common migraine: Italian cooperative trial. II. Long-term follow-up.	1985-05	3893736
Anticonvulsive properties of cinnarizine and flunarizine in rats and mice.	1975-09	1242663

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 `Mon Mar 31 18:23:48 GMT 2025` Edited by `admin` on `Mon Mar 31 18:23:48 GMT 2025`
Record UNII	R7PLA2DM0J
Record Status	`Validated (UNII)`
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Name

Type

Language

FLUNARIZINE

Official Name

English

SIBELIUM

Preferred 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

Classification Tree Code System Code

NCI_THESAURUS

C29578