Use of aminoguanidine or aminoguanidine analogs for the treatment of diseases of the nervous system

Abstract

The present invention relates to the use of aminoguanidine compounds for treating diseases of the nervous system. Aminoguanidine compounds can be used as therapeutically effective agents against a variety of diseases of the nervous system such as diabetic and toxic neuropathies, peripheral nervous system diseases, Alzheimer's disease, Parkinson's disease, stroke, Huntington's disease, amyotropic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, dysmyelination and demyelination disorders, and mitochondrial diseases. The aminoguanidine compounds which can be used in the present method include (1) aminoguanidine and diaminoguanidine analogs which can act as substrates or substrate analogs for creatine kinase; (2) bisubstrate inhibitors of creatine kinase comprising covalently linked structural analogs of adenosine triphosphate (ATP) and aminoguanidine; (3) aminoguanidine analogs which can act as reversible or irreversible inhibitors of creatine kinase; and (4) N-phosphoroaminoguanidine analogs bearing nontransferable moieties which mimic the N-phosphoryl group.

What is claimed is:  
     
         1 . A method for treating a subject afflicted with a nervous system disease comprising 
 administering to a subject a therapeutically effective amount of an aminoguanidine or a salt thereof, sufficient to prevent, reduce, ameliorate or eliminate a nervous system disease, such that treatment of said disease occurs.    
     
     
         2 . The method of  claim 1 , wherein said subject is a mammal.  
     
     
         3 . The method of  claim 1 , wherein said subject is human.  
     
     
         4 . A method for treating a subject for a disease of the nervous system comprising: 
 administering a therapeutically effective amount of an aminoguanidine to a subject such that said subject is treated for a disease of the nervous system, wherein said aminoguanidine has the formula:                        wherein 
 a) R 1  through R 16 , if present, are selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, and alkoxyl;  
                     
 d) T, if present, is R 12  or NR 13 R 14 ;  
 e) Y is an alkylene, alkenylene, alkynylene or an alkoxylene;  
 f) Z is selected from the group consisting of  
                     wherein B 1 -B 4  are each independently selected from hydrogen and OX 4  and X 1 -X 4  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl and pharmaceutically acceptable salts; and    wherein Y and Q or N and Q can form a ring structure.    
     
     
     
         5 . The method of  claim 4 , wherein said treatment comprises reducing or eliminating symptoms associated with a preexisting disease of the nervous system.  
     
     
         6 . The method of  claim 4 , wherein said treatment comprises preventing the occurrence of diseases of the nervous system within said subject.  
     
     
         7 . The method of  claim 4 , wherein said aminoguanidine compound is  
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 4 , wherein said aminoguanidine compound is  
       
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 4 , wherein said aminoguanidine compound is  
       
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 4 , wherein said aminoguanidine compound is  
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 4 , wherein said aminoguanidine compound is  
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 4 , wherein said disease of the nervous system is selected from the group consisting of neuropathies, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotropic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, acute disseminated encephalomyelitis, acute necrotizing hemorrhagic leukoencephalitis, dysmyelination disease, mitochondrial disease, migrainous disorder, bacterial infection, fungal infection, stroke, aging, dementia, peripheral nervous system diseases and mental disorders such as depression and schizophrenia.  
     
     
         13 . The method of  claim 12 , wherein said aminoguanidine is selected from the group  
       
         
           
           
               
               
           
         
       
     
     
         14 . The method of  claim 4 , further comprising coadministering to said subject a neurotransmitter, a neurotransmitter analog, a steroid, an immunomodulating agent, or an immune suppressive agent.  
     
     
         15 . The method of  claim 4 , wherein said subject is treated for diseases of the nervous system by reducing or eliminating symptoms associated with a preexisting disease of the nervous system.  
     
     
         16 . The method of  claim 4 , wherein said subject is treated for a disease of the nervous system by preventing occurrence of said disease of the nervous system within said subject.  
     
     
         17 . A method for alleviating toxic side effects of drugs used to treat a nervous system disease in a subject, comprising administering to a subject a therapeutically effective amount of an aminoguanidine or a pharmaceutically acceptable salt thereof, sufficient to prevent, reduce, ameliorate or alleviate toxic side effects of a drug used to treat a nervous system disease in said subject.  
     
     
         18 . The method of  claim 17 , wherein said aminoguanidine is selected from the group