Delivery of modulators of glutamate-mediated neurotransmission to the inner ear

Abstract

The invention features methods and devices for local delivery of agents that modify glutamate-mediated neurotransmission to the inner ear for treatment of inner ear disorders caused by glutamate-induced hearing loss and/or tinnitus.

1 . A pharmaceutical composition for treating an inner ear disorder, the composition comprising an agent that modulates glutamate-mediated neurotransmission or sodium channel function without causing significant clinical hearing loss associated with suppression of AMPA receptor-mediated signals. 
   
   
       2 . The pharmaceutical composition of  claim 1 , wherein the agent inhibits pre-synaptic release of glutamate. 
   
   
       3 . The pharmaceutical composition of  claim 1 , wherein the agent inhibits glutamate-mediated neurotransmission post-synaptically. 
   
   
       4 . The pharmaceutical composition of  claim 1 , wherein the agent is a glutamate ionotropic receptor antagonist. 
   
   
       5 . The pharmaceutical composition of  claim 4 , wherein the glutamate ionotropic receptor antagonist is an NMDA receptor antagonist. 
   
   
       6 . The pharmaceutical composition of  claim 5 , wherein the NMDA receptor antagonist is selected from the group consisting of: D-AP5, MK 801, 7-chlorokynurenate, gacyclidine, and derivatives or analogues thereof. 
   
   
       7 . A system for delivery of a drug to the round window membrane of the inner ear to treat an inner ear disorder, wherein the system comprises a sustained-release drug delivery device and a drug, and wherein the drug modulates glutamate-mediated neurotransmission without causing significant clinical hearing loss associated with suppression of AMPA receptor-mediated signals, and wherein the drug is delivered to the round window membrane over a period of at least 24 hours. 
   
   
       8 . The system of  claim 7  wherein the drug is an NMDA receptor antagonist. 
   
   
       9 . The system of  claim 8  wherein the NMDA receptor antagonist is selected from the group consisting of: D-AP5, MK 801, 7-chlorokynurenate, gacyclidine, and derivatives or analogues thereof. 
   
   
       10 . The system of  claim 8  wherein the drug delivery device comprises a pump 
   
   
       11 . The system of  claim 8  wherein the drug delivery device comprises a catheter. 
   
   
       12 . The system of  claim 8 , wherein the drug is delivered at a rate of from about 0.1 mg per hour to 200 mg per hour for a period of at least 24 hours. 
   
   
       13 . The system of  claim 8 , wherein the drug is delivered to the round window membrane of the inner ear for a period of at least about 3 days. 
   
   
       14 - 18 . (canceled)