Betahistine metabolites, Aminoethylpyridine, and Hydroxyethylpyridine increase cochlear blood flow in guinea pigs in vivo

Abstract

Objective: Betahistine is a histamine-like drug that is used in the treatment of Ménière's disease. It is commonly believed that betahistine increases cochlear blood flow and thus decreases the endolymphatic hydrops that is the cause of Ménière's. Despite common clinical use, there is little understanding of the kinetics or effects of its metabolites. This study investigated the effect of the betahistine metabolites aminoethylpyridine, hydroxyethylpyridine, and pyridylacetic acid on cochlear microcirculation. Design: Guinea pigs were randomly assigned to one of the groups: placebo, betahistine, or equimolar amounts of aminoethylpyridine, hydroxyethylpyridine, or pyridylacetic acid. Cochlear blood flow and mean arterial pressure were recorded for three minutes before and 15 minutes after treatment. Study sample: Thirty Dunkin-Hartley guinea pigs assigned to one of five groups with six guinea pigs per group. Results: Betahistine, aminoethylpyridine, and hydroxyethylpyridine caused a significant increase in cochlear blood flow in comparison to placebo. The effect seen under aminoethylpyridin was greatest. The group treated with pyridylacetic acid showed no significant effect on cochlear blood flow. Conclusion: Aminoethylpyridine and hydroxyethylpyridine are, like betahistine, able to increase cochlear blood flow significantly. The effect of aminoethylpyridine was greatest. Pyridylacetic acid had no effect on cochlear microcirculation.

Key Words::

• Betahistine
• histamine
• aminoethylpyridine
• hydroxyethylpyridine
• pyridylacetic acid
• cochlear blood flow
• Ménière's disease

Acknowledgements

This work is part of the doctoral thesis of Mattis Bertlich. The authors Mattis Bertlich and Fritz Ihler contributed equally to this study.

Declaration of interest: This project was supported by funds from the Deutsche Forschungsgemeinschaft to Prof. Canis under the grant code CA 629/2-1. The authors Bertlich, Ihler, Weiss, Sharaf, and Canis declare that they have no conflicts of interest. Prof. Strupp declares to have received funds in return for consulting services to Abbott, Pierre-Fabre, and Biogen Idec, as well as having received funds for the preparation of scientific training for Abbott, Biogen Idec, CSC, Henning Pharma, and GSK.