Ototoxicity of indacrinone is stereospecific.
Indacrinone (MK-196) is a loop diuretic which consists of a racemic mixture. The purpose of this study was to evaluate the individual enantiomers in the chinchilla model to determine whether these compounds affect auditory function and whether a difference in ototoxic potency exists. Very little change of endocochlear potential (EP) or compound action potential (CAP) was noted in animals receiving the (+)-enantiomer. On the other hand, chinchillas injected with the (-)-enantiomer were found to have a dose related reduction in both CAP and EP. These findings suggest the possibility that the diuretic receptor in the kidney and the receptor mediating ototoxicity in the cochlea, may have similar steric requirements for interacting with loop diuretics.
Rybak
L P
LP
Dept. of Surgery, SIU School of Medicine, Springfield, Illinois 62708.
Whitworth
C
C
D000818:Animals; D002682:Chinchilla; D003051:Cochlea / Q000187:drug effects*; D003055:Cochlear Microphonic Potentials; D004232:Diuretics / Q000633:toxicity*; D007189:Indans / Q000633:toxicity*; D007192:Indenes / Q000633:toxicity*; D013237:Stereoisomerism
D004232:Diuretics; D007189:Indans; D007192:Indenes; C013352:indacrinone