Flunarizine

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Flunarizine
Clinical data
Trade namesSibelium, others
Other names1-[bis(4-fluorophenyl)methyl]-4-cinnamyl-piperazine
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • C
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding>99%
MetabolismMainly CYP2D6
Metabolites≥15
Elimination half-life5–15 hrs (single dose)
18–19 days (multiple doses)
ExcretionFeces, <1% urine
Identifiers
  • 1-[bis(4-fluorophenyl)methyl]-4-[(2E)-3-phenylprop-2-en-1-yl]piperazine
JSmol)
Melting point251.5 °C (484.7 °F) (dihydrochloride)
  • Fc1ccc(cc1)C(c2ccc(F)cc2)N3CCN(CC3)C\C=C\c4ccccc4
  • 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+ checkY
  • Key:SMANXXCATUTDDT-QPJJXVBHSA-N checkY
  (verify)

Flunarizine, sold under the brand name Sibelium among others, is a drug classified as a

Janssen Pharmaceutica
(R14950) in 1968.

Medical uses

Flunarizine is effective in the prophylaxis of

vertigo of central and peripheral origin,[3] and as an add-on in the treatment of epilepsy where its effect is weak and not recommended.[4]
It has been shown to significantly reduce headache frequency and severity in both adults and children.

Contraindications

Flunarizine is

arrhythmia.[citation needed
]

Side effects

Common side effects include drowsiness (20% of patients), weight gain (10%), as well as extrapyramidal effects and depression in elderly patients.[3]

Interactions

The effects of other

pharmacokinetic interactions have been described.[3][5]

Pharmacology

Mechanism of action

Flunarizine is a selective calcium antagonist with moderate other actions including

intracellular mechanism such as antagonising calmodulin, a calcium binding protein.[3]

Pharmacokinetics

Flunarizine is well absorbed (>80%) from the gut and reaches maximal

steady state is reached after five to eight weeks. Concentrations in the brain are about ten times higher than in the plasma.[3][5]

It is metabolised in the liver, mainly by the enzyme

Elimination half life varies widely between individuals and is about 5 to 15 hours after a single dose, and 18 to 19 days on average when given daily.[3][5]

Chemistry

Flunarizine is a

derivative related to the antihistamines hydroxyzine and cinnarizine
(an older molecule also discovered by Janssen).

Research

Flunarizine may help to reduce the severity and duration of attacks of paralysis associated with the more serious form of alternating hemiplegia, as well as being effective in rapid onset dystonia-parkinsonism (RDP). Both these conditions arise from specific mutations in the ATP1A3 gene.[6][7]

Flunarizine extended motor neuron survival in spinal cord, protected skeletal muscles from cell death and atrophy and extended survival by 40% in an animal model of spinal muscular atrophy.[8] Flunarizine has also shown promise as an anti-prion medication.[citation needed]

References

  1. PMID 6487894
    .
  2. S2CID 36940918
    .
  3. ^
    ISBN 978-3-7741-9846-3
    .
  4. PMID 23543516
    .
  5. ^ a b c d Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  6. PMID 20301294
    .
  7. PMID 23622289
    .
  8. PMID 29391529
    .