Supplementary Material for: Histaminergic H3-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow

<p><br><strong><em>Objective:</em></strong> Betahistine is a histamine-like drug that is considered beneficial in Ménière's disease by increasing cochlear blood flow. Acting as an agonist at the histamine H<sub>1</sub>-receptor and as an inverse agonist at the H<sub>3</sub>-receptor, these receptors as well as the adrenergic α<sub>2</sub>-receptor were investigated for betahistine effects on cochlear blood flow. <b><i>Materials and Methods:</i></b> A total of 54 Dunkin-Hartley guinea pigs were randomly assigned to one of nine groups treated with a selection of H<sub>1</sub>-, H<sub>3</sub>- or α<sub>2</sub>-selective agonists and antagonists together with betahistine. Cochlear blood flow and mean arterial pressure were recorded for 3 min before and 15 min after infusion. <b><i>Results:</i></b> Blockage of the H<sub>3</sub>- or α<sub>2</sub>-receptors caused a suppression of betahistine-mediated typical changes in cochlear blood flow or blood pressure. Activation of H<sub>3</sub>-receptors caused a drop in cochlear blood flow and blood pressure. H<sub>1</sub>-receptors showed no involvement in betahistine-mediated changes of cochlear blood flow. <b><i>Conclusion:</i></b> Betahistine most likely affects cochlear blood flow through histaminergic H<sub>3</sub>-heteroreceptors.</p>