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 a disorder or condition selected from the group consisting of Down's syndrome; demyelinating diseases such as multiple sclerosis (MS) and amylolateral sclerosis (ALS); ophthalmic diseases such as dry eye syndrome, conjunctivitis, vernal conjunctivitis, and the like; ophthalmic conditions associated with cell proliferation such as proliferative vitreoretinopathy; substance-related disorders arising from the use of alcohol, amphetamines (or amphetamine-like substances) caffeine, cannabis, cocaine, hallucinogens, inhalants and aerosol propellants, nicotine, opioids, phenylglycidine derivatives, sedatives, hypnotics, and anxiolytics, which substance-related disorders include dependence and abuse, intoxication, withdrawal, intoxication delirium and withdrawal delirium; and addiction disorders involving addictions to behaviors (e.g., addictions to gambling and other addictive behaviors) 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 pervasive development disorder, fibromyalgia, human immunodeficiency virus (HIV) infections; HIV encephalopathy; dissociative disorders such as body dysmorphic disorders; eating disorder such as anorexia and bulimia; ulcerative colitis; Crohn's disease; irritable bowel syndrome; chronic fatigue syndrome; sudden infant death syndrome (SIDS); overactive bladder; lower urinary tract symptoms of overactive bladder; chronic cystitis; chemotherapy induced cystitis; itch, hiccups, premenstrual syndrome, premenstrual dysphoric disorder, amenorrheic disorders such as desmenorrhea; autism, attention deficit hyperactivity disorder (ADHD), angiogenesis (i.e., use for the inhibition of angiogenesis), Reiter's syndrome, anthropathies, reflex sympathetic dystrophy such as shoulder/hand syndrome; plasma extravasation resulting from cytokine chemotherapy; disorders of bladder function such as chronic cystitis, bladder detrusor hyper-reflexia, the urinary tract and urinary incontinence, including urinary urge incontinence, stress incontinence and mixed incontinence; fibrosing and collagen diseases such as scleroderma and eosinophilic fascioliasis; blood flow disorders caused by vasodilation and vasospastic diseases such as angina and Reynaud's disease; and male erectile dysfunction 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 gastrointestinal (GI) disorders, including inflammatory gastrointestinal disorders such as inflammation bowel disease, disorders caused by helicobacterpylori and diseases of the GI tract such as gastritis, proctitis, gastroduodenal ulcers, peptic ulcers, dyspepsia, disorders associated with the neuronal control of viscera, ulcerative colitis, chronic pancreatitis, Crohn's disease, irritable bowel syndrome and emesis, including post operative nausea and post operative vomiting, and including acute, delayed or anticipatory emesis (emesis includes emesis induced by chemotherapy, radiation, toxins, viral or bacterial infections, pregnancy, vestibular disorders, for example, motion sickness, vertigo, dizziness and Meniere's disease, surgery, migraine, variations in intercranial pressure, gastro-oesophageal reflux disease, acid indigestion, over indulgence in food or drink, acid stomach, waterbrash or regurgitation, heartburn, for example, episodic, nocturnal or meal-induced heartburn, and dyspepsia) 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.