Betahistine
Encyclopedia
Betahistine hydrochloride (brand names Serc, Hiserk, Betaserc) is an antivertigo
drug. It was first registered in Europe in 1970 for the treatment of Ménière's disease
. It is commonly prescribed to patients with balance disorder
s or to alleviate vertigo symptoms associated with Ménière's disease
.
. Its structure closely resembles that of phenethylamine
and histamine
.
is 3–4 hours, and excretion is virtually complete in the urine
within 24 hours. Plasma protein 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.
Betahistine seems to dilate the blood vessels within the middle ear which can relieve pressure from excess fluid and act on the smooth muscle.
Betahistine has two modes of action. Primarily, it has a direct stimulating (agonistic) effect on 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.
In addition, betahistine has a powerful antagonistic effects at H3 receptors, and increases the levels of neurotransmitters released from the nerve endings. This is thought to have two consequences;
Digestive Side Effects
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 and stomach cramping. These symptoms are usually not serious and subside in 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 possibly find a suitable alternative.
Other Side Effects
Patients 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 convulsions, daytime sleepiness, confusion and hallucinations. Some nervous system events may also partly be attributable to the underlying condition rather than the medication used to treat it. Other side effects listed in the package insert include low blood pressure and heart rhythm irregularities. 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.
Read more: http://www.livestrong.com/article/270761-betahistine-hydrochloride-side-effects/#ixzz1QmvDG2WD
http://www.livestrong.com/article/270761-betahistine-hydrochloride-side-effects/
s or tumours of the adrenal gland
, such as pheochromocytoma
. People with bronchial asthma should be closely monitored.
A recent Phase II clinical trial of the new drug in the U.S. suggests that women under the age of 50 who took Histalean (Betahistine) for 12 weeks lost 7 times the weight of those taking a placebo. What's most important to the researchers involved is that none of the 281 patients, males and females aged 18–65, complained of any serious side effects. The recent results were based on a double-blind, placebo-controlled study on people with a Body Mass Index ranging from 30 to 40. (A BMI of 30 and above indicate obesity.) The study was conducted at 19 investigation sites across the U.S. over a 12 week treatment period. The subgroup of high-dose Histalean (Betahistine)-treated women lost an average of 2.91% of their weight versus placebo group which lost only 0.4 %.
Betahistine is being studied for the treatment of atypical depression
at dosages from 50–300 mg/day due to its ability to antagonise H3 receptors and thus increase the release of serotonin
and dopamine
from nerve endings into the synaptic cleft.
Vertigo (medical)
Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...
drug. It was first registered in Europe in 1970 for the treatment of Ménière's disease
Ménière's disease
Ménière's disease is a disorder of the inner ear that can affect hearing and balance to a varying degree. It is characterized by episodes of vertigo and tinnitus and progressive hearing loss, usually in one ear. It is named after the French physician Prosper Ménière, who, in an article published...
. It is commonly prescribed to patients with balance disorder
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...
s or to alleviate vertigo symptoms associated with Ménière's disease
Ménière's disease
Ménière's disease is a disorder of the inner ear that can affect hearing and balance to a varying degree. It is characterized by episodes of vertigo and tinnitus and progressive hearing loss, usually in one ear. It is named after the French physician Prosper Ménière, who, in an article published...
.
Chemistry
Betahistine chemically is 2-[2-(methylamino)ethyl]pyridine, and is formulated as the dihydrochloride saltSalt
In chemistry, salts are ionic compounds that result from the neutralization reaction of an acid and a base. They are composed of cations and anions so that the product is electrically neutral...
. Its structure closely resembles that of phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...
and histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
.
Pharmacokinetics
Betahistine comes in tablet form and is taken orally. It is rapidly and completely absorbed. The mean plasma half-lifeHalf-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
is 3–4 hours, and excretion is virtually complete in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
within 24 hours. Plasma protein 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.
Mode of action
Betahistine has a very strong affinity as an antagonist for histamine H3 receptors and a weak affinity as an agonist for histamine H1 receptors.Betahistine seems to dilate the blood vessels within the middle ear which can relieve pressure from excess fluid and act on the smooth muscle.
Betahistine has two modes of action. Primarily, it has a direct stimulating (agonistic) effect on 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.
In addition, betahistine has a powerful antagonistic effects at H3 receptors, and increases the levels of neurotransmitters released from the nerve endings. This is thought to have two consequences;
- The increased amounts of histamine released from histaminergic nerve endings can stimulate H1 receptors, thus augmenting the direct agonistic effects of betahistine on these receptors. This explains the potent vasodilatory effects of betahistine in the inner ear, which are well documented.
- It is postulated that betahistine increases the levels of neurotransmitters such as serotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
in the brainstem, which inhibits the activity of vestibular nucleiVestibular nucleiThe vestibular nuclei are the cranial nuclei for the vestibular nerve.In Terminologia Anatomica they are grouped in both the pons and medulla.-Subnuclei:There are 4 subnuclei; they are situated at the floor of the fourth ventricle....
.
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.
- Decreased appetite, leading to weight loss
- Patients taking betahistine hydrochloride 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 hydrochloride 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 labored 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 Side Effects
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 and stomach cramping. These symptoms are usually not serious and subside in 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 possibly find a suitable alternative.
Other Side Effects
Patients 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 convulsions, daytime sleepiness, confusion and hallucinations. Some nervous system events may also partly be attributable to the underlying condition rather than the medication used to treat it. Other side effects listed in the package insert include low blood pressure and heart rhythm irregularities. 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.
Read more: http://www.livestrong.com/article/270761-betahistine-hydrochloride-side-effects/#ixzz1QmvDG2WD
http://www.livestrong.com/article/270761-betahistine-hydrochloride-side-effects/
Contraindications
Betahistine is contraindicated for people with peptic ulcerPeptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
s or tumours of the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
, such as pheochromocytoma
Pheochromocytoma
A pheochromocytoma or phaeochromocytoma is a neuroendocrine tumor of the medulla of the adrenal glands , or extra-adrenal chromaffin tissue that failed to involute after birth and secretes excessive amounts of catecholamines, usually noradrenaline , and adrenaline to a lesser extent...
. People with bronchial asthma should be closely monitored.
Experimental uses
A new use for betahistine may be in the field of obesity management. Dr Nir Barak of the Rabin Medical Centre in Tel Aviv has undertaken trials and it is reported (Telegraph, UK, 19 February 2007) that volunteers lost more than 1.5 kg/week over twelve weeks and experienced a distaste for fatty foods.A recent Phase II clinical trial of the new drug in the U.S. suggests that women under the age of 50 who took Histalean (Betahistine) for 12 weeks lost 7 times the weight of those taking a placebo. What's most important to the researchers involved is that none of the 281 patients, males and females aged 18–65, complained of any serious side effects. The recent results were based on a double-blind, placebo-controlled study on people with a Body Mass Index ranging from 30 to 40. (A BMI of 30 and above indicate obesity.) The study was conducted at 19 investigation sites across the U.S. over a 12 week treatment period. The subgroup of high-dose Histalean (Betahistine)-treated women lost an average of 2.91% of their weight versus placebo group which lost only 0.4 %.
Betahistine is being studied for the treatment of atypical depression
Atypical depression
Atypical depression is a subtype of dysthymia and major depression, sharing many of the symptoms of both, but also being characterized by mood reactivity—being able to experience improved mood in response to positive events. In contrast, sufferers of "melancholic" depression generally cannot...
at dosages from 50–300 mg/day due to its ability to antagonise H3 receptors and thus increase the release of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
from nerve endings into the synaptic cleft.