Betahistine

Clinical data
Trade names	Serc, others
AHFS/Drugs.com	International Drug Names
Routes of administration	By mouth Pregnancy category= c(risk not ruled out)
ATC code	N07CA01 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	~100%[1]
Protein binding	<5%[1]
Metabolism	Liver[1]
Metabolites	• 2-(2-Aminoethyl)pyridine • 2-Pyridylacetic acid[1]
Onset of action	<1 hour (peak)[2]
Elimination half-life	3.5 hours[3]
Excretion	Urine: 91%[1]
Identifiers
IUPAC name methyl[2‐(pyridin‐2‐yl)ethyl]amine
CAS Number	5638-76-6 Y
PubChem CID	2366
DrugBank	DB06698 Y
ChemSpider	2276 Y
UNII	X32KK4201D
KEGG	D07522 Y
ChEBI	CHEBI:35677 Y
ChEMBL	ChEMBL24441 Y
CompTox Dashboard (EPA)	DTXSID3022665
ECHA InfoCard	100.024.625
Chemical and physical data
Formula	C8H12N2
Molar mass	136.198 g·mol−1
3D model (JSmol)	Interactive image
SMILES n1ccccc1CCNC
InChI InChI=1S/C8H12N2/c1-9-7-5-8-4-2-3-6-10-8/h2-4,6,9H,5,7H2,1H3 Y Key:UUQMNUMQCIQDMZ-UHFFFAOYSA-N Y
(verify)

Betahistine, sold under the brand name Serc among others, is an anti-vertigo medication. It is commonly prescribed for balance disorders or to alleviate vertigo symptoms. It was first registered in Europe in 1970 for the treatment of Ménière's disease, but current evidence does not support its efficacy in treating it.^[4][5]

Medical uses

Betahistine was once believed to have some positive effects in the treatment of Ménière's disease and vertigo,^[3] but more recent evidence casts doubt on its efficacy.^[4][5] Studies of the use of betahistine have shown a reduction in symptoms of vertigo and, to a lesser extent, tinnitus, but conclusive evidence is lacking at present.

Oral betahistine has been approved for the treatment of Ménière's disease and vestibular vertigo in more than 80 countries worldwide, and has been reportedly prescribed for more than 130 million patients. However, betahistine has not been approved for marketing in the United States for the past few decades, and there is disagreement about its efficacy.

The Cochrane Library concluded in 2001 that "Most trials suggested a reduction of vertigo with betahistine and some suggested a reduction in tinnitus but all these effects may have been caused by bias in the methods. One trial with good methods showed no effect of betahistine on tinnitus compared with placebo in 35 patients. None of the trials showed any effect of betahistine on hearing loss. No serious adverse effects were found with betahistine."

Betahistine is also undergoing clinical trials for the treatment of attention deficit hyperactivity disorder (ADHD).^[6]

Contraindications

Betahistine is contraindicated for patients with pheochromocytoma. Patients with bronchial asthma or a history of peptic ulcer need to be closely monitored.^{[citation needed]}

Adverse effects

Patients taking betahistine may experience the following adverse effects:^[7]

• Headache
• Low level of gastric adverse effects
• Nausea can be an adverse effect, but patients are often already experiencing nausea owing to vertigo, so it goes largely unnoticed.
• Patients taking betahistine may experience hypersensitivity and allergic reactions. In the November 2006 issue of "Drug Safety", Dr. Sabine Jeck-Thole and Dr. Wolfgang Wagner reported that betahistine may cause allergic and skin-related adverse effects. These include rashes in several areas of the body; itching and urticaria (hives); and swelling of the face, tongue, and mouth. Other hypersensitivity reactions reported include tingling, numbness, burning sensations, shortness of breath, and laboured breathing. The study authors suggested that hypersensitivity reactions may be a direct result of betahistine's role in increasing histamine concentrations throughout the body. Hypersensitivity reactions quickly subside after betahistine has been discontinued.

Digestive

Betahistine may also cause several digestive-related adverse effects. The package insert for Serc, a trade name for betahistine, states that patients may experience several gastrointestinal side effects. These may include nausea, upset stomach, vomiting, diarrhea, dry mouth, and stomach cramping. These symptoms are usually not serious and subside between doses. Patients experiencing chronic digestive problems may lower their dose to the minimum effective and may mitigate the effects by taking betahistine with meals. Additional digestive problems may require that patients consult their physician in order to find a possible suitable alternative.

Others

People taking betahistine may experience several other adverse effects ranging from mild to serious. The package insert for Serc states that patients may experience nervous-system side effects, including headache. Some nervous system events may also partly be attributable to the underlying condition, rather than the medication used to treat it. Jeck-Thole and Wagner also reported that patients may experience headache and liver problems, including increased liver enzymes and bile-flow disturbances. Any adverse effects that persist or outweigh the relief of symptoms of the original condition may warrant that the patient consult their physician to adjust or change the medication.

Pharmacology

Pharmacodynamics

Betahistine is a strong antagonist at histamine H₃ receptors and a weak agonist at histamine H₁ receptors.^[1]

Betahistine has two mechanisms of action. Primarily, it is a weak agonist at histamine H₁ receptors located on blood vessels in the inner ear. This gives rise to local vasodilatation and increased permeability, which helps to reverse the underlying problem of endolymphatic hydrops.

More importantly, betahistine has a powerful antagonistic effect at histamine H₃ receptors, thereby increasing the amounts of the neurotransmitters histamine, acetylcholine, norepinephrine, serotonin, and GABA released from nerve endings. The increased amounts of histamine released from histaminergic nerve endings can stimulate histamine receptors. This stimulation explains the potent vasodilatory effects of betahistine in the inner ear, which are well documented.

Betahistine seems to dilate blood vessels in the inner ear, which can relieve pressure from excess fluid and act on the smooth muscle.

It is postulated that the increase in the amount of serotonin in the brainstem caused by betahistine inhibits the activity of vestibular nuclei.

Pharmacokinetics

Betahistine comes in both a tablet form and as an oral solution, and is taken orally. It is rapidly and completely absorbed. The mean plasma elimination half-life is 3 to 4 hours, and excretion is virtually complete in the urine within 24 hours. Plasma protein binding is very low. Betahistine is converted to aminoethylpyridine and hydroxyethylpyridine and excreted in the urine as pyridylacetic acid. There is some evidence that one of these metabolites, aminoethylpyridine, may be active and have effects similar to those of betahistine on ampullar receptors.^[8]

Chemistry

Betahistine chemically is 2-[2-(methylamino)ethyl]pyridine, and is formulated as the dihydrochloride salt. Its chemical structure closely resembles those of phenethylamine and histamine.^{[citation needed]}

Society and culture

Brand names

Betahistine is marketed under a number of brand names, including Veserc, Serc, Hiserk, Betaserc, and Vergo.^{[citation needed]}

Availability

Betahistine is widely used and available in Europe, including in the United Kingdom.^[1] It was approved by the US Food and Drug Administration in the early 1970s for Ménière's disease, but approval was later withdrawn because of lack of evidence of efficacy. The withdrawal was upheld by a US court of appeal in 1968.^{[citation needed]}