Flunarizine

Structural formula
General
Non-proprietary name	Flunarizine
other names	1- [bis (4-fluorophenyl) methyl] -4 - [(2 E ) -3-phenylprop-2-en-1-yl] piperazine ( IUPAC )
Molecular formula	C 26 H 26 F 2 N 2 (flunarizine) ; C 26 H 26 F 2 N 2 2HCl (flunarizine di hydrochloride ) ;
External identifiers / databases
EC number	257-937-5
ECHA InfoCard	100.052.652
PubChem	941361
ChemSpider	819216
DrugBank	DB04841
Wikidata	Q416237
Drug information
ATC code	N07 CA03
Drug class	Calcium antagonist
Mechanism of action	Calcium channel inhibitors
properties
Molar mass	404.49 g · mol -1 (flunarizine) ; 477.42 g · mol -1 (Flunarizine · dihydrochloride) ;
Physical state	firmly
Melting point	251.5 ° C (flunarizine dihydrochloride)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	960 mg kg −1 ( LD 50 , mouse , oral ) ; 285 mg kg −1 ( LD 50 , mouse , oral , dihydrochloride) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Flunarizine is a drug that is used in the preventive treatment of migraines and in the treatment of dizziness. Flunarizine is a calcium channel blocker which also has effects as an H ₁ antihistamine , anticonvulsant and antiarrhythmic . Flunarizine also acts as a FIASMA (functional inhibitor of acid sphingomyelinase ). The drug was discovered in 1967 by the pharmaceutical company Janssen Pharmaceutica .

Clinical information

Indications (areas of application)

Flunarizine is approved for the prophylaxis of a diagnosed migraine with or without aura if the frequency or severity of the migraine causes a corresponding level of distress. In addition, there is a pharmaceutical approval for the symptomatic treatment of vertigo as a result of a persistent disturbance of the organ of equilibrium . It is recommended as a prophylactic agent for migraine-like syndromes in adolescents.

Contraindications (contraindications)

Flunarizine must not be used in patients with a known intolerance to the active substance, Parkinson's disease or a history of other extrapyramidal motor disorders. Flunarizine is also contraindicated in patients with a history of known depressive syndromes.

Interactions

If taken at the same time as alcohol or drugs with a sedative effect - such as sedatives or tranquilizers - the sedative side effects of flunarizine can be increased.

Adverse drug effects

Fatigue, increased appetite and weight gain were the most common side effects in over 10% of patients. Occasionally (0.1–1% of patients) additional central nervous side effects such as insomnia and anxiety have been reported. Gastrointestinal side effects such as heartburn, nausea and stomach pain, as well as headache and asthenia can occur just as frequently. Galactorrhea , dry mouth, muscle pain and skin reddening have been described in very rare cases (<0.01%).

Rare but serious side effects can occur during long-term treatment with flunarizine. These include depressive moods and Parkinson's-like symptoms, such as extrapyramidal motor disorders, bradykinesia , rigidity , tremor , orofacial dyskinesia , akinesia and akathisia . In these cases, further treatment with flunarizine should be discontinued.

Trade names

Monopreparations : Flunavert (D), Natil-N (D), Sibelium (A, D, CH), Generika (D) The commercial preparations contain flunarizine dihydrochloride.

Individual evidence

^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; Pp. 708-709, ISBN 978-0-911910-00-1 .
↑ ^a ^b data sheet Flunarizine dihydrochloride from Sigma-Aldrich , accessed on April 1, 2011 ( PDF ).
↑ ^a ^b entry on flunarizine. In: Römpp Online . Georg Thieme Verlag, accessed on November 11, 2014.
↑ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .
↑ ^a ^b ^c ^d Specialist information Natil ^® -N 5 mg / 10 mg. Hormosan Pharma GmbH. As of October 2008.
↑ Therapy of idiopathic headaches in childhood and adolescence Guideline of the German Migraine and Headache Society (DMKG) and the Society for Neuropediatrics: Nervenheilkunde 2008; 27: 1127-1137. Retrieved February 8, 2018.
↑ ROTE LISTE 2008 , Verlag Rote Liste Service GmbH, Frankfurt am Main, ISBN 978-3-939192-20-6 .

[MERCK_Index-1] The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; Pp. 708-709, ISBN 978-0-911910-00-1 .

[Sigma-2] ta sheet Flunarizine dihydrochloride from Sigma-Aldrich , accessed on April 1, 2011 ( PDF ).

[RÖMPP_Online-3] try on flunarizine. In: Römpp Online . Georg Thieme Verlag, accessed on November 11, 2014.

[pmid18504571-4] Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .

[FI_Natil-5] Specialist information Natil ^® -N 5 mg / 10 mg. Hormosan Pharma GmbH. As of October 2008.

[6] Therapy of idiopathic headaches in childhood and adolescence Guideline of the German Migraine and Headache Society (DMKG) and the Society for Neuropediatrics: Nervenheilkunde 2008; 27: 1127-1137. Retrieved February 8, 2018.

[ROTE_LISTE-7] ROTE LISTE 2008 , Verlag Rote Liste Service GmbH, Frankfurt am Main, ISBN 978-3-939192-20-6 .