Different action of memantine and caroverine on glutamatergic transmission in the mammalian cochlea.
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.
Oestreicher
Elmar
E
ENT Department, Technical University of Munich, Germany. e.oestreicher@lrz.tum.de
Ehrenberger
Klaus
K
Felix
Dominik
D
D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism*; D015259:Dopamine Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism; D008559:Memantine / Q000493:pharmacokinetics / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism; D011810:Quinoxalines / Q000493:pharmacokinetics / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D015259:Dopamine Agents; D011810:Quinoxalines; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008559:Memantine; C000957:caroverine