Cochlear effects of indacrinone are not altered by penicillin

Abstract

Indacrinone is a loop diuretic structurally related to ethacrynic acid. Indacrinone is a racemic mixture. Previous studies have shown that the (−) enantiomer caused reduction of endocochlear potential (EP) and elevation of compound action potential (CAP) threshold (Rybak and Whitworth, 1987a). It has been demonstrated that organic acids such as penicillin, probenecid and sodium salicylate prevent the reduction of EP normally observed after furosemide administration (Rybak et al., 1992a). The present study was designed to determine whether penicillin pretreatment could prevent changes in EP and CAP threshold in (−)-indacrinone treated chinchillas. Adult chinchillas were anesthetized with ketamine and pentobarbital. A microelectrode was advanced into the scala media using the round window approach, and CAP responses to clicks were measured. One group was treated with (−)-indacrinone 100 mg/kg via the jugular vein. A second group of animals received penicillin 50 mg/kg IV thirty minutes before (−)-indacrinone. The mean EP change in the indacrinone-treated animals was 38.38 ± 19.32 millivolts (mv). The reduction of EP in the group receiving penicillin was 24.43 ± 20.74 mv ( P > 0.09). The mean CAP threshold changes in animals receiving indacrinone was 20 ± 14.14 dB whereas those pretreated with penicillin showed a threshold shift of 21.43 ± 20.35 dB ( P > 0.05). These findings are consistent with previous studies which showed that the effect of ethacrynic acid on the EP and CAP was not changed by the pretreatment with penicillin (Rybak et al., 1990).