Methods for the treatment of tinnitus induced by cochlear excitotoxicity

Abstract

The invention relates to methods for the prevention and/or treatment of tinnitus induced by cochlear excitotoxicity. In these methods, a pharmaceutical composition comprising an NMDA receptor antagonist is administered to an individual in need of such treatment by appropriate devices and/or formulations for local administration to the inner ear. The tinnitus to be prevented and/or treated may be provoked by acoustic trauma, presbycusis, ischemia, anoxia, treatment with one or more ototoxic medications, sudden deafness, or other cochlear excitotoxic-inducing occurrence. The invention also relates to method for the identification of compounds effective in the treatment and prevention of tinnitus by a novel screening method incorporating an electrophysiological test method.

1 . A method of reducing the perception of tinnitus in a human in need thereof comprising administering to the human a pharmaceutical composition comprising ketamine. 
     
     
         2 . The method of  claim 1 , wherein the tinnitus is acute. 
     
     
         3 . The method of  claim 1 , wherein the tinnitus results from acoustic trauma, presbycusis, ischemia, anoxia, infection, exposure to ototoxic drugs, or sudden deafness. 
     
     
         4 . The method of  claim 1 , wherein the tinnitus results from an occurrence that induces cochlear excitotoxicity. 
     
     
         5 . The method of  claim 1 , wherein the tinnitus persists for more than 24 hours. 
     
     
         6 . The method of  claim 1 , wherein the pharmaceutical composition comprises a ketamine analog, a ketamine derivative, a ketamine enantiomer, or pharmaceutically acceptable salt thereof. 
     
     
         7 . The method of  claim 6 , wherein the ketamine enantiomer is (S)-ketamine or pharmaceutically acceptable salt thereof. 
     
     
         8 . The method of  claim 6 , wherein the pharmaceutically acceptable salt is hydrochloride salt. 
     
     
         9 . The method of  claim 1 , wherein the pharmaceutical composition is a gel. 
     
     
         10 . The method of  claim 9 , wherein the gel is a hyaluronate gel. 
     
     
         11 . The method of  claim 1 , wherein the pharmaceutical composition is administered topically via the round window membrane or the oval window membrane to the inner ear. 
     
     
         12 . The method of  claim 1 , wherein the pharmaceutical composition is administered by a transtympanic injection. 
     
     
         13 . The method of  claim 1 , wherein the pharmaceutical composition is delivered to the middle ear. 
     
     
         14 . A method of ameliorating persistent tinnitus in a human in need thereof comprising administering to the human a pharmaceutical composition comprising ketamine. 
     
     
         15 . The method of  claim 14 , wherein the tinnitus is acute. 
     
     
         16 . The method of  claim 14 , wherein the tinnitus results from acoustic trauma, presbycusis, ischemia, anoxia, infection, exposure to ototoxic drugs, or sudden deafness. 
     
     
         17 . The method of  claim 14 , wherein the tinnitus results from an occurrence that induces cochlear excitotoxicity. 
     
     
         18 . The method of  claim 14 , wherein the tinnitus persists for more than 24 hours. 
     
     
         19 . The method of  claim 14 , wherein the pharmaceutical composition comprises a ketamine analog, a ketamine derivative, a ketamine enantiomer, or pharmaceutically acceptable salt thereof. 
     
     
         20 . The method of  claim 19 , wherein the ketamine enantiomer is (S)-ketamine or pharmaceutically acceptable salt thereof. 
     
     
         21 . The method of  claim 19 , wherein the pharmaceutically acceptable salt is hydrochloride salt. 
     
     
         22 . The method of  claim 14 , wherein the pharmaceutical composition is a gel. 
     
     
         23 . The method of  claim 22 , wherein the gel is a hyaluronate gel. 
     
     
         24 . The method of  claim 14 , wherein the pharmaceutical composition is administered topically via the round window membrane or the oval window membrane to the inner ear. 
     
     
         25 . The method of  claim 14 , wherein the pharmaceutical composition is administered by a transtympanic injection. 
     
     
         26 . The method of  claim 14 , wherein the pharmaceutical composition is delivered to the middle ear.