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

Objective: Betahistine is a histamine-like drug that is considered beneficial in Meniere's disease by increasing cochlear blood flow. Acting as an agonist at the histamine H-1-receptor and as an inverse agonist at the H-3-receptor, these receptors as well as the adrenergic alpha(2)-receptor were investigated for betahistine effects on cochlear blood flow. Materials and Methods: A total of 54 Dunkin-Hartley guinea pigs were randomly assigned to one of nine groups treated with a selection of H-1-, H-3- or alpha(2)-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. Results: Blockage of the H-3- or alpha(2)-receptors caused a suppression of betahistine-mediated typical changes in cochlear blood flow or blood pressure. Activation of H-3-receptors caused a drop in cochlear blood flow and blood pressure. H-1-receptors showed no involvement in betahistine-mediated changes of cochlear blood flow. Conclusion: Betahistine most likely affects cochlear blood flow through histaminergic H-3-heteroreceptors. (C) 2015 S. Karger AG, Basel