Methods for treating channelopathies

Abstract

The present invention is directed to the use of a class of peptide compounds for treating diseases associated with hyperexcitability. The present invention is also directed to the use of a class of peptide compounds for treating diseases associated with dysfunction of an ion channel.

1 - 68 . (canceled) 
     
     
         69 . A method for alleviating and/or treating a channelopathy in a subject in need thereof, comprising administering to the subject a compound of Formula II 
       
         
           
           
               
               
           
         
         wherein 
         Ar is aryl, which is unsubstituted or substituted with at least one electron-donating group and/or at least one electron-withdrawing group; 
         R 1  is alkyl; and 
         R 3  is selected from the group consisting of hydrogen, alkyl, arylalkyl, alkoxy, alkoxyalkyl, aryl, a heterocyclic group, heterocyclic alkyl, N-alkoxy-N-alkylamino, N-alkoxyamino, and N-carbalkoxy; or a pharmaceutically acceptable salt thereof; 
         wherein the channelopathy is an epilepsy syndrome. 
       
     
     
         70 . The method of  claim 69 , wherein, in the compound of Formula II, R 3  is —CH 2 — alkoxy and/or R 1  is methyl. 
     
     
         71 . The method of  claim 69 , wherein, in the compound of Formula II, Ar is phenyl which is unsubstituted or substituted with at least one halo group. 
     
     
         72 . The method of  claim 69 , wherein said compound is
 (R)-2-acetamido-N-benzyl-3-methoxypropionamide;   (R)-2-acetamido-N-benzyl-3-ethoxypropionamide;   O-methyl-N-acetyl-D-serine-m-fluorobenzylamide; or   O-methyl-N-acetyl-D-serine-p-fluorobenzylamide.   
     
     
         73 . The method of  claim 69 , wherein the compound is in the R configuration. 
     
     
         74 . The method of  claim 69 , wherein the compound is lacosamide. 
     
     
         75 . The method of  claim 69 , wherein the epilepsy syndrome is a disease associated with dysfunction of a voltage-gated ion channel or a ligand-gated ion channel. 
     
     
         76 . The method of  claim 69 , further comprising administering to the subject at least one further active agent for alleviation and/or treatment of a channelopathy. 
     
     
         77 . The method of  claim 69 , wherein the epilepsy syndrome is associated with a mutation at SCN1A, SCN2A, CACNB4, KCNQ2, KCNQ3 or CHRNA4. 
     
     
         78 . The method of  claim 69 , wherein the epilepsy syndrome is selected from the group consisting of generalized epilepsy with febrile seizures plus, severe myoclonic epilepsy in infancy, benign familial neonatal infantile seizure, intractable childhood epilepsy with generalized tonic-clonic seizure and infantile spasms. 
     
     
         79 . The method of  claim 69 , wherein the epilepsy syndrome is selected from the group consisting of benign familial neonatal convulsions 1, benign familial neonatal convulsions 2 and nocturnal frontal lobe epilepsy. 
     
     
         80 . The method of  claim 69 , wherein the compound of Formula (II) or a pharmaceutically acceptable salt thereof is administered in a dosage amount of 50 mg/day to 1000 mg/day. 
     
     
         81 . The method of  claim 69 , wherein the compound of Formula (II) or a pharmaceutically acceptable salt thereof is administered in a dosage amount of 200 mg/day to 600 mg/day.