Ototoxic side-effects of the I(Ks)-channel blocker HMR1556.
The inhibitor of I(Ks)-channels, HMR1556, a potentially antiarrhythmic drug, might possess ototoxic side-effects. The I(Ks)-channels are not only expressed in the heart but also in the stria vascularis of the inner ear and in the dark cells of the vestibular organ. Therefore possible effects of HMR1556 on hearing were studied in cats. Thresholds and intensity function of the cochlear action potential (CAP) were used as criteria. In addition to effects of the drug on heart rate and ECG, a substantial elevation of hearing thresholds and a shift in CAP intensity functions were observed. There was a clear dose-effect relationship. The hearing impairment observed showed a tendency for recovery. It is concluded that inhibitors of I(Ks)-channels may generally exert ototoxic effects provided they can reach the cochlear spaces.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002415:Cats; D002839:Chromans / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000503:physiopathology*; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000633:toxicity*; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides / Q000633:toxicity*
D002839:Chromans; C420023:HMR 1556; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; C059983:potassium channel protein I(sk)