Betahistine, sold under the brand name Serc among others, is an

anti-vertigo medication Vertigo is a condition in which a person has the sensation that they are moving, or that objects around them are moving, when they are not. Often it feels like a spinning or swaying movement. It may be associated with nausea, vomiting, perspira ...

. 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. Equilibr ...

s or to alleviate

vertigo Vertigo is a condition in which a person has the sensation that they are moving, or that objects around them are moving, when they are not. Often it feels like a spinning or swaying movement. It may be associated with nausea, vomiting, perspira ...

symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

s. 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 in ...

and

, but more recent evidence casts doubt on its efficacy. Studies of the use of betahistine have shown a reduction in symptoms of vertigo and, to a lesser extent,

tinnitus Tinnitus is a condition when a person hears a ringing sound or a different variety of sound when no corresponding external sound is present and other people cannot hear it. Nearly everyone experiences faint "normal tinnitus" in a completely ...

, 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 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 systema ...

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." An intranasal formulation of betahistine dihydrochloride received

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

designation from the US

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 respo ...

(FDA) for the treatment of obesity associated with

Prader–Willi syndrome Prader–Willi syndrome (PWS) is a rare genetic disorder caused by a loss of function of specific genes on chromosome 15. In newborns, symptoms include hypotonia, weak muscles, poor feeding, and slow development. Beginning in childhood, those ...

, a rare genetic disorder. 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 symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...

(ADHD).

Contraindications

Betahistine is contraindicated for patients with

pheochromocytoma Pheochromocytoma is a rare tumor of the adrenal medulla composed of chromaffin cells and is part of the paraganglioma (PGL) family of tumors, being defined as an intra-adrenal PGL. These neuroendocrine tumors can be sympathetic, where they relea ...

. Patients with bronchial asthma or a history of

peptic ulcer Peptic ulcer disease is when the inner part of the stomach's gastric mucosa (lining of the stomach), the first part of the small intestine, or sometimes the lower esophagus, gets damaged. An ulcer in the stomach is called a gastric ulcer, while ...

need to be closely monitored.

Adverse effects

Patients taking betahistine may experience the following adverse effects: * 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 weak

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

at histamine H₃ receptors and a weak partial agonist at histamine H₁ receptors. Betahistine primarily acts on histamine H₁ receptors located on blood vessels in the inner ear, leading to vasodilation and increased vascular permeability. These effects help to alleviate endolymphatic hydrops, a key factor in

. Additionally, betahistine interacts with histamine H₃ receptors as a weak antagonist or inverse agonist. By modulating H₃ receptors, betahistine increases the release of various

neurotransmitters A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotransmitters are rele ...

, including

histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

, and

GABA GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

from nerve endings. This mechanism contributes to improved blood flow in the inner ear and modulation of vestibular compensation. Betahistine's effects on neurotransmitter release, particularly serotonin, may also play a role in its modulation of vestibular nuclei activity in the brainstem. These combined actions help alleviate symptoms associated with vestibular disorders.

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 Biological half-life (elimination half-life, pharmacological 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 blood plasma. ...

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

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

within 24 hours.

Plasma protein Plasma proteins, sometimes referred to as blood proteins, are proteins present in blood plasma. They perform many different functions, including transport of hormones, vitamins and minerals in activity and functioning of the immune system. Other b ...

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.

Chemistry

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

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

. Its

chemical structure A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...

closely resembles those of

phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace ami ...

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 over 115 countries worldwide, 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 Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

United States

Betahistine, marketed as Serc, received initial approval from the US Food and Drug Administration (FDA) in November 1966 for the treatment of Ménière's disease. This approval was based on a single clinical study conducted by Joseph Elia and published in the ''

Journal of the American Medical Association ''JAMA'' (''The Journal of the American Medical Association'') is a peer-reviewed medical journal published 48 times a year by the American Medical Association. It publishes original research, reviews, and editorials covering all aspects of ...

'' (JAMA) in April of that year. However, concerns soon arose regarding the study's methodology and the strength of its findings, with public criticism appearing in publications such as the '' Medical Letter on Drugs and Therapeutics''. This prompted an FDA investigation, culminating in the agency obtaining Elia's original study data in April 1967. Subsequent review of the data revealed inadequacies, leading the FDA to issue a notice of intent to withdraw approval in 1968. Instead of immediate withdrawal, the FDA engaged in discussions with Unimed, the manufacturer, regarding the design of a new clinical trial. This decision not to immediately remove betahistine from the market drew congressional scrutiny, particularly from Representative Lawrence Fountain, who cited the Food, Drug, and Cosmetic Act's mandate for withdrawal when substantial evidence of efficacy is lacking. Internal dissent within the FDA regarding the original approval and its reliance on a single study further complicated the situation. The controversy unfolded against the backdrop of the 1962 Kefauver–Harris Amendment, which had strengthened requirements for demonstrating drug efficacy. Ultimately, the FDA terminated betahistine's new drug application on December 21, 1972, following a lawsuit filed by

Consumers Union A consumer is a person or a group who intends to order, or use purchased goods, products, or services primarily for personal, social, family, household and similar needs, who is not directly related to entrepreneurial or business activities. Th ...

. Unimed's attempted legal challenge to maintain the drug's market presence was also unsuccessful, with the US Court of Appeals for the Second Circuit upholding the FDA's withdrawal. Betahistine remains unapproved by the FDA, although it is available through compounding pharmacies.

References

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