Abstract
ObjectiveBetahistine is a histamine H1-receptor agonist and H3-receptor antagonist that is administered to treat Menière’s disease. Despite widespread use, its pharmacological mode of action has not been entirely elucidated. This study investigated the effect of betahistine on guinea pigs at dosages corresponding to clinically used doses for cochlear microcirculation.MethodsThirty healthy Dunkin-Hartley guinea pigs were randomly assigned to five groups to receive betahistine dihydrochloride in a dose of 1,000 mg/kg b. w. (milligram per kilogram body weight), 0.100 mg/kg b. w., 0.010 mg/kg b. w., 0.001 mg/kg b. w. in NaCl 0.9% or NaCl 0.9% alone as placebo. Cochlear blood flow and mean arterial pressure were continuously monitored by intravital fluorescence microscopy and invasive blood pressure measurements 3 minutes before and 15 minutes after administration of betahistine.ResultsWhen betahistine was administered in a dose of 1.000 mg/kg b. w. cochlear blood flow was increased to a peak value of 1.340 arbitrary units (SD: 0.246; range: 0.933–1.546 arb. units) compared to baseline (p<0.05; Two Way Repeated Measures ANOVA/Bonferroni t-test). The lowest dosage of 0.001 mg/kg b. w. betahistine or NaCl 0.9% had the same effect as placebo. Nonlinear regression revealed that there was a sigmoid correlation between increase in blood flow and dosages.ConclusionsBetahistine has a dose-dependent effect on the increase of blood flow in cochlear capillaries. The effects of the dosage range of betahistine on cochlear microcirculation corresponded well to clinically used single dosages to treat Menière’s disease. Our data suggest that the improved effects of higher doses of betahistine in the treatment of Menière’s disease might be due to a corresponding increase of cochlear blood flow.
Highlights
In 1861 Prosper Meniere (1799–1862) described a typical combination of symptoms [1]
The Effect of Betahistine on Cochlear Microcirculation Administration of 0.001 and 0.010 mg betahistine/kg b. w. did not lead to significant changes in blood flow (Figure 1A, Figure 1B)
There was a further decrease in cochlear blood flow, but no more significant differences were observed (Figure 1C)
Summary
In 1861 Prosper Meniere (1799–1862) described a typical combination of symptoms (hearing loss, tinnitus, and attacks of vertigo) [1]. Meniere ascribed the condition to a lesion in the semicircular canals, thereby challenging the prevailing opinion that vertigo was a condition caused exclusively by pathologies of the central nervous system [2]. A wide range of treatment strategies is applied; reliable evidence of their efficacy is scarce for most of them, and their side effects are severe. They include diuretics [4], intratympanic application of gentamicin [5], steroids [6] or endolymphatic sac surgery [7]
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