Glutamate is the major transmitter candidate between inner hair cells and the afferent neurons of the mammalian cochlea. We investigated the action of memantine (1-amino-3,5-dimethyl-adamantane) and the quinoxaline derivative caroverine [1-diethylaminoethyl-3,8-(p-methoxybenzyl)-1,2-dihydro-quinoxaline-dione] on the glutamatergic transmission in the guinea pig cochlea utilizing extracellular recording techniques and microiontophoretic ejection of substances. While memantine was able to inhibit the NMDA (N-methyl-D-aspartate)-induced firing, the AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)-stimulated activity was unaffected. In contrast, caroverine could block both NMDA- as well as AMPA-induced firing. As memantine and caroverine are currently in clinical use, these substances could be introduced to the treatment of several cochlear disorders.