Betahistine

Adverse effects

Patients taking betahistine dihydrochloride may experience following side effects

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 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.

Other

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.

Contraindications

Betahistine is contraindicated for people with pheochromocytoma. People with bronchial asthma and history of peptic ulcer need to be closely monitored.

Chemistry

Betahistine chemically is 2-[2-(methylamino)ethyl]pyridine, and is formulated as the dihydrochloride salt. Its structure closely resembles that of phenethylamine and histamine.

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 half-life 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.

Mechanism 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 has two mechanisms of action. Primarily, it a full 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 histamine, acetylcholine, norepinephrine, 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.