Cochlear effects of two new loop diuretics

Abstract

Loop diuretics such as ethacrynic acid and furosemide have been shown in previous studies to alter cochlear function in animals and humans. Since the endocochlear potential of animals is reduced after administration of other loop diuretics, we have studied the effects of two newer loop diuretics, ozolinone and indacrinone, on this d.c. resting potential. Chinchillas weighing 400–600 g were anesthetized with pentobarbital 30 mg/kg and ketamine 45 mg/kg intramuscularly. The bulla was opened and the endocochlear potential (EP) was measured with a glass microelectrode placed through the round window. Control animals injected IV with vehicle had very little change of the EP. Doses of the diuretics ranging from 50–300 mg/kg were injected intravenously. Ozolinone had very little effect on the EP even at the highest dosage. On the other hand, indacrinone injection caused a dose‐dependent reduction of the endocochlear potential. It was interesting to note that the maximum effect of indacrinone did not occur until 20–30 min after injection. These findings suggest that the newer loop diuretics may act on the cochlea in a different manner. Some of these differences may be due to discrete mechanisms of drug distribution and metabolism. [Work supported by NIH.]