Description

Flunarizine, typically formulated as Flunarizine Dihydrochloride, is a medication classified as a selective calcium channel blocker and a antihistamine. It is a diphenylmethylpiperazine derivative. It is not available in the United States but is widely used in many other countries, particularly in Europe, Asia, and Latin America. Flunarizine is primarily known for its preventative properties rather than for the acute treatment of conditions.

Indications

Flunarizine is mainly used for the prophylactic (preventative) treatment of certain neurological and vascular conditions. Its main indications include:

• Migraine Prophylaxis: It is a key medication for the prevention of migraine headaches in patients who have frequent or severe attacks and who do not respond to or cannot tolerate other preventative treatments. It is not effective for the acute treatment of a migraine attack.
• Vertigo and Vestibular Disorders: It is used to manage and prevent symptoms of dizziness and vertigo, particularly those associated with vestibular system disorders, such as Meniere’s disease.

• Peripheral Vascular Disorders: In some regions, it is used to manage symptoms of certain peripheral vascular diseases where vasospasm is a component.

Mechanism of Action

The mechanism of action of flunarizine is complex and not fully understood, but it is primarily attributed to its ability to selectively block calcium channels and its antihistaminic properties.

1. Selective Calcium Channel Blockade: Flunarizine is a non-selective calcium channel blocker, but it has a high selectivity for calcium channels in the smooth muscles of the brain’s blood vessels. During a migraine attack, it is thought that abnormal calcium influx into these smooth muscle cells can lead to sustained vasodilation and inflammation. By blocking these calcium channels, flunarizine helps to prevent this vasodilation, thereby reducing the frequency and severity of migraine attacks. It is believed to act on the calcium channels on the cell membrane, which play a role in regulating blood vessel tone.
2. Antihistamine Action: Flunarizine is also a potent antagonist of histamine H1 receptors. This action is responsible for some of its side effects, such as sedation and drowsiness, but it is also thought to contribute to its anti-vertigo and anti-migraine effects by modulating histamine’s role in the vestibular system and brain.
3. Other Effects: Flunarizine also has other actions that may contribute to its therapeutic profile:
   • It blocks the entry of sodium into cells.
   • It has some mild serotonin antagonism, particularly at the 5-HT2A receptor.

• • It protects brain cells from oxygen deprivation.

In summary, flunarizine prevents migraine attacks by stabilizing vascular tone and preventing excessive vasodilation. Its dual action as a calcium channel blocker and an antihistamine, combined with other less understood effects, makes it a unique and effective prophylactic agent for migraines and vertigo.