Serc (betahistine)

Last Updated: 1/03.

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Timothy C. Hain, MD

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This drug (brand name Serc, chemical name betahistine), is advocated as a vestibular suppressant mainly for Meniere's disease. Curiously, Serc was approved by the FDA about 30 years ago for roughly 5 years, but later approval was withdrawn because lack of evidence for efficacy. Subsequently, three double-blind studies have been done reporting reduction of vertigo attacks with betahistine (Frew and Menon, 1976: Wilmot and Menon; 1976; Meyer, 1985). Nevertheless, these studies may have been flawed and a recent review suggested that it is presently still unclear if betahistine has any effect in Meniere's disease (James and Burton, 2001).

Serc was again reviewed by the FDA in June of 1999 (click here for details). Essentially, the conclusion seems to be that there is no evidence that it is harmful, but also little evidence that it has any therapeutic effect. It thus is similar in status to an inert substance. Serc is not sold through ordinary US pharmacy chains but it can be obtained through US compounding pharmacies, with a prescription. Some insurances may cover it too.

Betahistine can also be easily obtained through US compounding pharmacies and also from overseas pharmacies. Many of these pharmacies will accept prescriptions via fax and mail medication. An example is


Betahistine is a histamine agonist. There are 3 histamine receptors - -H1, H2 and H3. The rationale for its use is somewhat difficult to understand as H1 blocking antihistamines (such as meclizine) are also used quite commonly to treat vertigo. Explanations commonly given are that the drug is a vasodilator, or that it acts on subreceptors of histamine. H1 and H2 are post-synaptic receptors and H3 is a pre-synaptic receptor. Betahistine is a potent H3 receptor antagonist. (Lacour and Sterkers, 2001). Stimulation of the H3 receptor reduces histamine release, so antagonism of H3 increases histamine release. H3 receptors control the synthesis and release of histamine via a Gs protein (de Waele et al, 1995).

According to de Waele et al (1995), there are several lines of evidence that suggest that histamine receptors modulate the function of central vestibular neurons. One influence is via axons from the posterior hypothalamus. This may be related to wakefulness as histamine controls wakefulness. Both H1 and H2 binding sites have been detected in vestibular nuclei. These authors note that there is data suggesting both that H1 and H2 actions are excitatory on the vestibular nucleus, and that common H2 blocker drugs such as cimetidine antagonize the effect. This suggests that H2 blockers, at least those that cross into the brain, may have a central suppressant effect. H3 antagonists appear to inhibit horizontal vestibular gain without affecting alertness.

Most antivertigo drugs such as meclizine are H1 blockers. Many allergy medications are selective peripheral H1 blockers and many medications for stomach problems that block acid are H2 blockers, but these are not generally thought to affect vestibular function. Betahistine is an H3 antagonist, according to Timmerman (1991). H3 antagonism is felt to increase H1 and H2, so the net effect of H3 antagonism is histamine agonism. Confusingly though, some authors suggest that betahistine is an H3 agonist. The neuropharmacological literature is also complex. Arrang et al (1985) found betahistine to be a partial agonist against cerebral H1 receptors, and has no effect on H3 receptors. In other words, some H3 agonists might block histamine release, but betahistine (betahistine) doesn't affect these receptors in guinea-pigs. This would suggest that either betahistine is a placebo, or that it's effects result from some mechanism other than H3.

As mentioned above, it seems contradictory that both H1 blockers (meclizine) and H1 agonists (betahistine) are advocated for vertigo. It, however, is possible that the antihistamine effects of meclizine are less important than its anticholinergic effects, so there may not be a contradiction between the H1 effects. The general thought at the present is that the effects of betahistine relate to it's effect on H3 receptors, although what exactly this effect is still rather mysterious. If betahistine is indeed an H1 agonist and an H3 antagonist, it might suppress vestibular function and enhance alertness, both valuable qualities. By this thinking, betahistine could be reasonably combined with a selective H2 blocker that does not cross into the brain. Is it reasonable to combine meclizine (a central H1 blocker) and betahistine (a central H1 agonist) ? Well, perhaps if you are hoping to use the central anticholinergic properties of meclizine. It would see a more logical, however, to use a pure anticholinergic agent such as scopolamine instead of meclizine. Similarly, it does not seem all that unreasonable to combine betahistine with a contemporary non-sedating antihistamine, as these medications do not cross the blood brain barrier.

Does it work ?

The author of this review has had moderate success with giving betahistine to patients who have intractable Meniere's disease, and it part of his usual regimen for intractable Meniere's. The usual dose is 8-16 mg 3-4 times per day. Most people that report a positive effect can decide this with a few days -- it doesn't seem to take 1 month to figure out whether betahistine is helping or not.

There are numerous puzzling aspects to betahistine and the jury is still out regarding whether or not it is an effective medication. Some studies report that betahistine cannot be distinguished from placebo. There are also some troublesome reports comparing betahistine to other medications that are almost certainly placebos, that can be interpreted in the same way. Klein et al (1998) reported that a homeopathic medication was equivalent in efficacy to betahistine. As homeopathic medications are generally felt to be placebos because of the extremely high dilutions with which they are administered, this suggests that either the Klein study was flawed, or that betahistine is also a placebo. On the other hand, Fujino et al (1994) reported betahistine to have a positive effect when combined with rehabilitation.

Side Effects

Side-effects are generally minimal but the author of this review has encountered stomach upset in several, worsening asthma, headache, and chest tightness as side-effects. Of course, these symptoms could be found to a placebo. In theory, stomach upset might be related to H2 agonism, as H2 blockers are used to treat gastric acidity. Against this idea is that betahistine is not a H1 agonist, but the increased release of histamine associated with h3 antagonism might stimulate H2. As mentioned above, it seems reasonable to combine betahistine with a selective H2 blocker that does not cross the blood brain barrier, or a proton pump inhibitor used for gastric acidity. Headache might also be a direct effect of histamine. See this outside link for more information.

In it's favor, Betahistine does not cause drowsiness and has no effect on driving, reaction time or visual acuity (Betts et al, 1991)