title: Concentration-Response Relationship of Hearing Impairment Caused by Quinine and Salicylate: Pharmacological Similarities but Different Molecular Mechanisms.
abstract: This review has the purpose to summarize concentration-effect studies made with quinine and to compare the effects on hearing between quinine and salicylate. Quinine and salicylate have roles in experimental hearing research and may induce pronounced and reversible hearing impairment when administered in sizeable doses. The quinine-induced increase in hearing threshold and its recovery can be analysed according to 'the psychophysical power function'. The power function is a special case of the Hill equation when the stimulus (e.g. a drug concentration) is exceedingly small compared with the concentration that would elicit a half-maximum response. Quinine and salicylate induce sensorineural hearing impairment and tinnitus when given in higher dose ranges in man. The drugs influence the presence, magnitude, and quality of audiological responses, such as spontaneous and evoked otoacoustic emissions. Quinine reversibly reduces frequency selectivity and hearing sensitivity, whereas the self-attained most comfortable speech level and the acoustic stapedius reflex are not affected, that is the dynamic range of hearing is reversibly reduced. This observation supports the view that quinine acts on the outer hair cell of the cochlea. Both drugs share a protective effect against the permanent hearing damages caused by gentamicin. This action is interpreted as a request for functioning mechanoelectric transducer (MET) channels to elicit the ill effect of aminoglycosides. Both drugs may interfere with the cochlear amplifier through blocking MET channels and the motor protein prestin. This review finds considerable overlap between type and extent of pharmacological actions of quinine and salicylate, supposedly caused by partly shared mechanisms of action but performed with different molecular mechanisms.
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Alvan
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.|Department of Audiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Berninger
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Lars L
authors.initials: LL
authors.lastname: Gustafsson
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.|Department of Audiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kjell K
authors.initials: KK
authors.lastname: Karlsson
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.|Laboratory of Pharmacology-Toxicology, Tours University Hospital, Tours, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Paintaud
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Monique
authors.initials: M
authors.lastname: Wakelkamp
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000962:Antimalarials / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D015394:Molecular Structure; D011803:Quinine / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D012459:Salicylates / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D012720:Severity of Illness Index; D014012:Tinnitus / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000962:Antimalarials; D012459:Salicylates; D011803:Quinine; D001241:Aspirin