Method and composition for treating irritable bowel syndrome using low doses of opioid receptor antagonists

Abstract

This invention relates to a method for treating a subject with irritable bowel syndrome (“IBS”) which comprises long-term administration of an opioid receptor antagonist at an appropriately low dose which will selectively antagonize excitatory opioid receptor functions, but not inhibitory opioid receptor functions, in myenteric neurons in the intestinal tract as well as in neurons of the central nervous system (“CNS”). The administration of the opioid receptor antagonist at a low dose enhances the potency of the inhibitory effects of endogenous opioid peptides present in the intestinal tract and the CNS, thereby reducing abdominal pain and stool frequency resulting from abnormally supersensitized excitatory opioid receptor functions. The invention also relates to a composition for treating a subject with IBS, which comprises an effective dose of an opioid receptor antagonist, and a pharmaceutically acceptable carrier.

1 . A method for treating irritable bowel syndrome in a subject in need of such treatment, comprising administering to said subject an amount of an excitatory opioid receptor antagonist effective to treat irritable bowel syndrome in said subject.  
     
     
         2 . The method according to  claim 1 , wherein said amount of the excitatory opioid receptor antagonist is effective to block at least one of hypersensitivity and hyperexcitability of visceral sensory and visceral motor neurons associated with irritable bowel syndrome.  
     
     
         3 . The method according to  claim 1 , wherein said amount of the excitatory opioid receptor antagonist is effective to treat abdominal pain and at least one of abnormal consistency and abnormal frequency of stools in said subject.  
     
     
         4 . The method according to  claim 1 , wherein said excitatory opioid receptor antagonist is a member selected from the group consisting of naltrexone, nalmefene, diprenorphine, naloxone, etorphine, dihydroetorphine, biphalin, and similarly acting opioid alkaloids or peptides.  
     
     
         5 . The method according to  claim 1 , wherein said excitatory opioid receptor antagonist is naltrexone.  
     
     
         6 . The method according to  claim 5 , wherein said naltrexone is administered at a dose effective to relieve abdominal pain associated with IBS and wherein said dose is further ineffective to induce dysphoria.  
     
     
         7 . The method according to  claim 5 , wherein said naltrexone is administered at a dose between about 0.1 mg/day and about 5 mg/day.  
     
     
         8 . The method according to  claim 5 , wherein said naltrexone is administered at a dose between about 0.3 mg/day and about 3 mg/day.  
     
     
         9 . The method according to  claim 5 , wherein said naltrexone is administered at a dose between about 2 μg/kg body weight/day and about 70 μg/kg body weight/day.  
     
     
         10 . The method according to  claim 5 , wherein said naltrexone is administered at a dose between about 4 μg/kg body weight/day and about 45 μg/kg body weight/day.  
     
     
         11 . The method according to  claim 1 , wherein said excitatory opioid receptor antagonist is nalmefene.  
     
     
         12 . The method according to  claim 11 , wherein said nalmefene is administered at a dose effective to relieve abdominal pain associated with IBS and wherein said dose is further ineffective to induce dysphoria.  
     
     
         13 . The method according to  claim 11 , wherein said nalmefene is administered at a dose between about 0.01 mg/day and about 1 mg/day.  
     
     
         14 . The method according to  claim 1 , wherein said excitatory opioid receptor antagonist is administered in one or more forms selected from the group consisting of orally, parenterally, transdermally, or by suppository.  
     
     
         15 . The method according to  claim 1 , wherein said excitatory opioid receptor antagonist is administered orally.  
     
     
         16 . A pharmaceutical composition for treating irritable bowel syndrome in a subject in need of such treatment, comprising an amount of an excitatory opioid receptor antagonist effective to treat irritable bowel syndrome in said patient.  
     
     
         17 . The pharmaceutical composition according to  claim 16 , wherein said amount of the excitatory opioid receptor antagonist is effective to block at least one of hypersensitivity and hyperexcitability of visceral sensory and visceral motor neurons associated with irritable bowel syndrome.  
     
     
         18 . The pharmaceutical composition according to  claim 16 , wherein said amount of the excitatory opioid receptor antagonist is effective to treat abdominal pain and at least one of abnormal consistency and abnormal frequency of stools in said subject, and a pharmaceutically acceptable carrier.  
     
     
         19 . The pharmaceutical composition according to  claim 16 , wherein said excitatory opioid receptor antagonist is a member selected from the group consisting of naltrexone, nalmefene, diprenorphine, naloxone, etorphine, dihydroetorphine, biphalin, and similarly acting opioid alkaloids or peptides.  
     
     
         20 . The pharmaceutical composition according to  claim 16 , wherein said excitatory opioid receptor antagonist is naltrexone.  
     
     
         21 . The pharmaceutical composition according to  claim 20 , wherein said naltrexone is present at a dose effective to relieve abdominal pain associated with IBS and wherein said dose is further ineffective to induce dysphoria.  
     
     
         22 . The pharmaceutical composition according to  claim 20 , wherein said naltrexone is present at a dose between about 0.1 mg and about 5 mg.  
     
     
         23 . The pharmaceutical composition according to  claim 20 , wherein said naltrexone is present at a dose between about 0.3 mg and about 3 mg.  
     
     
         24 . The pharmaceutical composition according to  claim 16 , wherein said excitatory opioid receptor antagonist is nalmefene.  
     
     
         25 . The pharmaceutical composition according to  claim 24 , wherein said nalmefene is present at a dose effective to relieve abdominal pain associated with IBS and wherein said dose is further ineffective to induce dysphoria.  
     
     
         26 . The pharmaceutical composition according to  claim 24 , wherein said nalmefene is present at a dose between about 0.01 mg and about 1 mg.  
     
     
         27 . The pharmaceutical composition according to  claim 16 , wherein said pharmaceutical composition is in a form effective for administration to said patient by any member from the group consisting of orally, parenterally, transdermally, or by suppository.  
     
     
         28 . The pharmaceutical composition according to  claim 16 , wherein said excitatory opioid receptor is in a form effective to be administered orally.