Betahistine, sold under the brand name Serc among others, is an anti-vertigo medication. It is commonly prescribed for

balance disorder A balance disorder is a disturbance that causes an individual to feel unsteady, for example when standing or walking. It may be accompanied by feelings of giddiness, or wooziness, or having a sensation of movement, spinning, or floating. Balance ...

s or to alleviate

vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...

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.

Medical uses

Betahistine was once believed to have some positive effects in the treatment of

Ménière's disease Ménière's disease (MD) is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Typically, only one ear is affected initi ...

and

but more recent evidence casts doubt over its efficacy. There have been studies of the use of betahistine which showed a reduction in symptoms of vertigo and to a lesser extent,

tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...

, in subjects, 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 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 The Cochrane Library (named after Archie Cochrane) is a collection of databases in medicine and other healthcare specialties provided by Cochrane and other organizations. At its core is the collection of Cochrane Reviews, a database of system ...

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 Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...

(ADHD).

Contraindications

Betahistine is contraindicated for patients with

pheochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

. Patients with bronchial asthma or a history of

peptic ulcer Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines ...

need to be closely monitored.

Side effects

Patients taking betahistine may experience following side effects: * Headache * Low level of gastric side effects * Nausea can be a side effect, but the patient is generally already experiencing nausea due to the vertigo so it goes largely unnoticed. * Patients taking betahistine may experience several 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 several allergic and skin-related side effects. These include rash in several areas of the body; itching and 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 suggest that hypersensitivity reactions may be a direct result of betahistine's role in increasing histamine levels throughout the body. Hypersensitivity reactions quickly subside after betahistine has been discontinued.

Digestive

Betahistine may also cause several digestive-related side 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 range and 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 side 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. The study by Jeck-Thole and Wagner also reports that patients may experience headache and liver problems, including increased liver enzymes and bile-flow disturbances. Any side 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 of the

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered ...

H₃ receptor and a weak agonist of the histamine H₁ receptor. Betahistine has two mechanisms of action. Primarily, it is a weak agonist on the H₁ receptors located on blood vessels in the inner ear. This gives rise to local vasodilation and increased permeability, which helps to reverse the underlying problem of endolymphatic hydrops. More importantly, betahistine has a powerful antagonistic effects at H₃ receptors, thereby increasing the levels of neurotransmitters

, acetylcholine,

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...

, serotonin, and GABA released from the nerve endings. The increased amounts of histamine released from histaminergic nerve endings can stimulate receptors. This stimulation explains the potent vasodilatory effects of betahistine in the inner ear, that are well documented. Betahistine seems to dilate the blood vessels within the inner ear which can relieve pressure from excess fluid and act on the smooth muscle. It is postulated that betahistine's increase in the level of serotonin in the brainstem inhibits the activity of

vestibular nuclei The vestibular nuclei (VN) are the cranial nuclei for the vestibular nerve located in the brainstem. In Terminologia Anatomica they are grouped in both the pons and the medulla in the brainstem. Structure Path The fibers of the vestibular n ...

Pharmacokinetics

Betahistine comes in both a tablet form as well as an oral solution, and is taken orally. It is rapidly and completely absorbed. The mean plasma

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

is 3 to 4 hours, and excretion is virtually complete in the

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

within 24 hours.

Plasma protein Blood-proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood pr ...

binding is very low. Betahistine is transformed into aminoethylpyridine and hydroxyethylpyridine and excreted with the urine as pyridylacetic acid. There is some evidence that one of these metabolites, aminoethylpyridine, may be active and exert effects similar to those of betahistine on ampullar receptors.

Chemistry

Betahistine chemically is 2- -(methylamino)ethylyridine, and is formulated as the dihydrochloride

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

. Its

chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of ...

closely resembles those of phenethylamine and

Society and culture

Brand names

Betahistine is marketed under a number of brand names, including Veserc, Serc, Hiserk, Betaserc, and Vergo.

Availability

Betahistine is widely used and available in

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirel ...

, including in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the European mainland, continental mainland. It comprises England, Scotlan ...

. It was approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

in the early 1970s for Ménière's disease, but approval was later withdrawn for lack of evidence of efficacy. The withdrawal was upheld by a US court of appeals in 1968.

References

{{Histamine receptor modulators Amines H3 receptor antagonists Histamine agonists 2-Pyridyl compounds Vasodilators