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 associated with Ménière's disease. It was first registered in Europe in 1970 for the treatment of Ménière's disease. Betahistine is used in the treatment of Ménière's disease and vertigo.[3] The supporting evidence for the efficacy of Betahistine for Ménière's disease is of poor quality.[3] A 2011 Cochrane review of seven trials consisting of 243 patients with Ménière's disease concluded that there was insufficient evidence for any beneficial effect of Betahistine on symptoms.[3] Most of the trials found a reduction in symptoms of vertigo and to a lesser extent tinnitus, but these effects may have been due to bias in study methodology.[3] Betahistine is contraindicated for patients with pheochromocytoma. Patients with bronchial asthma or a history of peptic ulcer need to be closely monitored.[citation needed] Patients taking Betahistine may experience following side effects:[4] 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. 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. Betahistine is a strong antagonist of the histamine H3 receptor and a weak agonist of the histamine H1 receptor.[1] Betahistine has two mechanisms of action. Primarily, it is 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. 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 is 3 to 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.[5] 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] Betahistine is marketed under a number of brand names, including Veserc, Serc, Hiserk, Betaserc, Solvay, and Vergo.[citation needed] Betahistine is widely used and available in Europe, including in the United Kingdom.[1] It was approved by the Food and Drug Administration 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.[contradictory]