Pharmaceutical uses for alpha2delta ligands

Abstract

The invention relates to a method of treating central nervous system disorders and other disorders by administering an alpha2delta ligand such as, for example, a compound of the formula or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen or straight or branched lower alkyl, and n is an integer of from 4 to 6.

1 - 19 . (canceled)  
   
   
       20 . A method of treating pain due to spinal cord or brain stem damage in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.  
   
   
       21 . A method of treating a disorder or condition selected from the group consisting of neurodegenerative disorders, such as Parkinson's disease (PD), Huntington's disease (HD) and Alzheimer's disease (AD); delirium, dementias (e.g., senile dementia of the Alzheimer's type, senile dementia, vascular dementia, HIV-1 associated dementia, AIDS dementia complex (ADC), dementias due to head trauma, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, or due to multiple etiologies), amnestic disorders, other cognitive or memory disorders, and behavioral symptoms of dementia in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.  
   
   
       22 . A method of treating a disorder or condition selected from the group consisting of movement disorders such as primary movement disorders, akinesias, dyskinesias (e.g., familial paroxysmal dyskinesia, tardive dyskinesia, tremor, chorea, myoclonus, tics and other dyskinesias) spasticities, Tourette's syndrome, Scott syndrome, palsys (e.g., Bell's palsy, cerebral palsy, birth palsy, brachial palsy, wasting palsy, ischemic palsy, progressive bulbar palsy and other palsys), akinetic-rigid syndrome; extra-pyramidal movement disorders such as medication-induced movement disorders, for example, neuroleptic-induced Parkinsonism, neuroleptic malignant syndrome, neuroleptic-induced acute dystonia, neuroleptic-induced acute akathisia, neuroleptic-induced tardive dyskinesia and medication-induced postural tremour; restless legs syndrome and movement disorders associated with Parkinson's disease or Huntington's disease in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an alpha2delta ligand or a pharmaceutically acceptable salt thereof.  
   
   
       23 . A method according to  claim 20 , wherein the alpha2delta ligand is gabapentin.  
   
   
       24 . A method according to  claim 20 , wherein the alpha2delta ligand is pregabalin.  
   
   
       25 . A method according to  claim 20 , wherein the alpha2delta ligand is a compound of the formula X  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein 
 R 1  is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms;  
 R 2  is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms;  
 R 3  is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1  -C 3 )alkyl, phenyl, phenyl-(C 1 -C 3 )alkyl, pyridyl, pyridyl-(C 1 -C 3 )alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms, preferably with from zero to three fluorine atoms, and wherein said phenyl and said pyridyl and the phenyl and pyridyl moieties of said phenyl-(C 1 -C 3 )alkyl and said pyridyl-(C 1 -C 3 )alkyl, respectively, can be optionally substituted with from one to three substituents, preferably with from zero to two substituents, independently selected from chloro, fluoro, amino, nitro, cyano, (C 1 -C 3 )alkylamino, (C 1 -C 3 )alkyl optionally substituted with from one to three fluorine atoms and (C 1 -C 3 )alkoxy optionally substituted with from one to three fluorine atoms;  
 with the proviso that when R 1 is hydrogen, R 2  is not hydrogen.  
 
   
   
       26 . A method according to  claim 21 , wherein the alpha2delta ligand is gabapentin.  
   
   
       27 . A method according to  claim 21 , wherein the alpha2delta ligand is pregabalin.  
   
   
       28 . A method according to  claim 21 , wherein the alpha2delta ligand is a compound of the formula X  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein 
 R 1  is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms;  
 R 2  is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms;  
 R 3  is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 3 )alkyl, phenyl, phenyl-(C 1 -C 3 )alkyl, pyridyl, pyridyl-(C 1 -C 3 )alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms, preferably with from zero to three fluorine atoms, and wherein said phenyl and said pyridyl and the phenyl and pyridyl moieties of said phenyl-(C 1 -C 3 )alkyl and said pyridyl-(C 1 -C 3 )alkyl, respectively, can be optionally substituted with from one to three substituents, preferably with from zero to two substituents, independently selected from chloro, fluoro, amino, nitro, cyano, (C 1 -C 3 )alkylamino, (C 1 -C 3 )alkyl optionally substituted with from one to three fluorine atoms and (C 1 -C 3 )alkoxy optionally substituted with from one to three fluorine atoms;  
 with the proviso that when R 1  is hydrogen, R 2  is not hydrogen.  
 
   
   
       29 . A method according to  claim 22 , wherein the alpha2delta ligand is gabapentin.  
   
   
       30 . A method according to  claim 22 , wherein the alpha2delta ligand is pregabalin.  
   
   
       31 . A method according to  claim 22 , wherein the alpha2delta ligand is a compound of the formula X  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein 
 R 1  is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms;  
 R 2  is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms;  
 R 3  is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 3 )alkyl, phenyl, phenyl-(C 1 -C 3 )alkyl, pyridyl, pyridyl-(C 1 -C 3 )alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms, preferably with from zero to three fluorine atoms, and wherein said phenyl and said pyridyl and the phenyl and pyridyl moieties of said phenyl-(C 1 -C 3 )alkyl and said pyridyl-(C 1 -C 3 )alkyl, respectively, can be optionally substituted with from one to three substituents, preferably with from zero to two substituents, independently selected from chloro, fluoro, amino, nitro, cyano, (C 1 -C 3 )alkylamino, (C 1 -C 3 )alkyl optionally substituted with from one to three fluorine atoms and (C 1 -C 3 )alkoxy optionally substituted with from one to three fluorine atoms;  
 with the proviso that when R 1  is hydrogen, R 2  is not hydrogen.