title: Betahistine-induced vascular effects in the rat cochlea.
abstract: Betahistine (BH) has been used widely to treat cochlear disorders, such as tinnitus and Meniere's disease. The mechanism of action of BH in the cochlea is assumed to be based on its histamine-like effect on H1 receptors in the cochlear vasculature, leading to an increased cochlear blood flow (CBF). Recently it has been shown that BH can strongly affect H3 heteroreceptors (a novel histamine receptor subclass) in the periphery, via an autonomic ligand. This mechanism may also contribute to the BH effects on CBF. This study was to validate BH effects in the cochlear vasculature and to investigate the possible mechanisms of action of this drug in the inner ear vasculature. We assessed the effects of BH on CBF with the laser Doppler flowmeter in 23 rats and concluded that BH affects vascular conductivity in the cochlea in a dose-dependent fashion; betahistine diffuses through the round window, but does not have access to vascular receptors or ligands once in the labyrinthine fluids; and the H1 receptors mediate the systemic and peripheral vascular effects of BH, whereas the cochlear effect involves cholinergic receptors.
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48901-0506.
authors.forename: E A
authors.initials: EA
authors.lastname: Laurikainen
authors.forename: J M
authors.initials: JM
authors.lastname: Miller
authors.forename: W S
authors.initials: WS
authors.lastname: Quirk
authors.forename: J
authors.initials: J
authors.lastname: Kallinen
authors.forename: T
authors.initials: T
authors.lastname: Ren
authors.forename: A L
authors.initials: AL
authors.lastname: Nuttall
authors.forename: R
authors.initials: R
authors.lastname: Grénman
authors.forename: E
authors.initials: E
authors.lastname: Virolainen
mesh_terms: D000818:Animals; D001285:Atropine; D001621:Betahistine / Q000008:administration & dosage / Q000009:adverse effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003051:Cochlea / Q000098:blood supply / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D007262:Infusions, Intravenous; D017078:Laser-Doppler Flowmetry; D008297:Male; D011398:Promethazine; D051381:Rats
chemical_list: D001285:Atropine; D011398:Promethazine; D001621:Betahistine