Use and composition for treating myasthenia gravis and other myasthenic syndromes

Abstract

The present invention describes the use of a 5HT3-antagonist, in combination with pyridostigmine, to facilitate the symptomatic treatment of mammalian subjects, and particularly humans, dogs, and cats, suffering from a myasthenic syndrome, notably myasthenia gravis, by providing a therapeutically effective pyridostigmine bromide daily dose without the typical adverse effects.

1 . A method for safely improving the conditions of a mammal suffering from symptoms of muscle weakness associated with MG or another myasthenic syndrome, comprising chronically administering to said mammal a 5HT3-antagonist in combination with pyridostigmine. 
     
     
         2 . The method of  claim 1 , wherein said pyridostigmine is pyridostigmine bromide. 
     
     
         3 . The method of  claim 1 , wherein said 5HT3-antagonist is ondansetron or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         4 . The method of  claim 1 , wherein said 5HT3-antagonist is administered to said mammal at a single oral or subcutaneous dose of from 0.001 mg/kg to 1.8 mg/kg, given from one to three times per day, with a maximum of 300 mg/day. 
     
     
         5 . The method of  claim 1 , wherein said pyridostigmine in said combination is administered to said mammal at a single oral dose equivalent to from 0.5 mg/kg to 6 mg/kg of pyridostigmine bromide. 
     
     
         6 . The method according to  claim 1 , wherein said pyridostigmine in said combination is administered to said mammal in an unit form comprising an amount per unit form of said pyridostigmine equivalent to from 2 mg to 800 mg of pyridostigmine bromide. 
     
     
         7 . The method according to  claim 1 , wherein said pyridostigmine in said combination is administered to said mammal at a single subcutaneous dose equivalent to from 0.1 mg/kg to 1.2 mg/kg of pyridostigmine bromide. 
     
     
         8 . The method according to  claim 1 , wherein said pyridostigmine in said combination is administered to said mammal at a daily continuous infusion subcutaneous dose equivalent to from 0.5 mg/kg to 4 mg/kg of pyridostigmine bromide. 
     
     
         9 . The method according to  claim 1 , wherein the mammal is suffering from myasthenia gravis. 
     
     
         10 . The method according to  claim 9 , wherein the mammal is a human, dog or cat. 
     
     
         11 . The method according to  claim 10 , wherein the mammal is a human. 
     
     
         12 . A method for a myasthenic syndrome, comprising administering to a mammalian subject in need thereof, an effective daily dose of a combination comprising 5HT3-antagonist and pyridostigmine. 
     
     
         13 . A fixed-dose combination comprising a pharmaceutical or veterinary composition in dosage unit form comprising, as active ingredients, 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Component (a) 
                   a 5HT3-antagonist; and 
                 
                     
                   Component (b) 
                   pyridostigmine, 
                 
                     
                     
                 
             
                
               
               
                
                
                
               
            
           
         
       
       in admixture with a pharmaceutical carrier or vehicle. 
     
     
         14 . The fixed-dose combination of  claim 13 , wherein the 5HT3-antagonist Component (a) is present in an amount per unit form of from 1 mcg to 300 mg and the pyridostigmine Component (b) is present in an amount equivalent to of from 0.4 mg to 800 mg of pyridostigmine bromide.