Methods of treating gastrointestinal tract disorders using sodium channel modulators

Abstract

The invention relates to methods of using sodium channel modulators, particularly TTX-R sodium channel modulators and/or activity dependent sodium channel modulators to treat gastrointestinal tract disorders, particularly inflammatory bowel disorders and irritable bowel syndrome.

What is claimed is:  
     
         1 . A method for treating a GI tract disorder except for acid peptic disorders or structural gastroesophageal disorders, which comprises administering to an individual in need thereof a therapeutically effective amount of an active agent wherein said agent is a sodium channel modulator or a pharmaceutically acceptable salt, ester, amide, prodrug, or active metabolite thereof.  
     
     
         2 . The method of  claim 1 , wherein the active agent is contained within a pharmaceutical formulation.  
     
     
         3 . The method of  claim 2 , wherein the pharmaceutical formulation is a unit dosage formulation.  
     
     
         4 . The method of  claim 1 , wherein the active agent is administered on an as-needed basis.  
     
     
         5 . The method of  claim 1 , wherein the active agent is administered prior to commencement of an activity wherein suppression of the symptoms of a GI tract disorder except for acid peptic disorders or structural gastroesophageal disorders would be desirable.  
     
     
         6 . The method of  claim 1 , wherein the active agent is administered from about 0 minutes to about 3 hours prior to commencement of an activity wherein suppression of the symptoms of a GI tract disorder except for acid peptic disorders or structural gastroesophageal disorders would be desirable.  
     
     
         7 . The method of  claim 1 , wherein the formulation is a controlled release dosage formulation.  
     
     
         8 . The method of  claim 1 , wherein the formulation is a delayed release dosage formulation.  
     
     
         9 . The method of  claim 7 , wherein the formulation is a sustained release dosage formulation.  
     
     
         10 . The method of  claim 8 , wherein the formulation is a sustained release dosage formulation.  
     
     
         11 . The method of  claim 9 , wherein the sustained release dosage form provides drug release over a time period of from about 6 hours to about 8 hours.  
     
     
         12 . The method of  claim 1 , wherein the active agent is administered orally.  
     
     
         13 . The method of  claim 2 , wherein the active agent is administered orally.  
     
     
         14 . The method of  claim 13 , wherein the pharmaceutical formulation is selected from the group consisting of tablets, capsules, caplets, solutions, suspensions, syrups, granules, beads, powders and pellets.  
     
     
         15 . The method of  claim 1 , wherein the active agent is administered transmucosally.  
     
     
         16 . The method of  claim 15 , wherein the active agent is administered sublingually.  
     
     
         17 . The method of  claim 15 , wherein the active agent is administered buccally.  
     
     
         18 . The method of  claim 15 , wherein the active agent is administered intranasally.  
     
     
         19 . The method of  claim 15 , wherein the active agent is administered transurethrally.  
     
     
         20 . The method of  claim 15 , wherein the active agent is administered rectally.  
     
     
         21 . The method of  claim 15 , wherein the active agent is administered by inhalation.  
     
     
         22 . The method of  claim 1 , wherein the active agent is administered topically.  
     
     
         23 . The method of  claim 1 , wherein the active agent is administered transdermally.  
     
     
         24 . The method of  claim 1 , wherein the active agent is administered parenterally.  
     
     
         25 . The method of  claim 1 , wherein the active agent is administered intrathecally.  
     
     
         26 . The method of  claim 1 , wherein the GI tract disorder is selected from the group consisting of inflammatory bowel disorders and irritable bowel syndrome.  
     
     
         27 . The method of  claim 26 , wherein the inflammatory bowel disorder is selected from the group consisting of Crohn's disease, ulcerative colitis, collagenous colitis, lymphocytic colitis, and proctitis.  
     
     
         28 . The method of  claim 1 , wherein said sodium channel modulator is: 
 a. a TTX-R sodium channel modulator, or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof; or    b. an activity-dependent sodium channel modulator, or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.    
     
     
         29 . The method of  claim 26 , wherein said TTX-R sodium channel modulator is: 
 a. a compound that interacts with Na v 1.8 channels, or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof; or    b. a compound that interacts with Na v 1.9 channels, or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.    
     
     
         30 . The method of  claim 1 , wherein said sodium channel modulator is Ralfinamide or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.  
     
     
         32 . The method of  claim 1 , wherein said sodium channel modulator is Ambroxol or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.  
     
     
         33 . The method of  claim 1 , wherein said sodium channel modulator is Sipatrigine or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.  
     
     
         34 . The method of  claim 1 , wherein said sodium channel modulator is Lamotrigine or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.  
     
     
         35 . The method of  claim 2 , wherein the pharmaceutical formulation further comprises an additional active agent.  
     
     
         36 . The method of  claim 35 , wherein the additional active agent is selected from the group consisting of: an antispasmodic, a tricyclic antidepressant, duloxetine, venlafaxine, a monoamine reuptake inhibitor, a spasmolytic, an anticholinergic, gabapentin, pregabalin, a substituted aminomethyl-phenyl-cyclohexane derivative, a 5-HT 3  antagonist, a 5-HT 4  antagonist, a β3 adrenergic agonist, a neurokinin receptor antagonist, a bradykinin receptor antagonist, a nitric oxide donor, and derivatives thereof.  
     
     
         37 . A pharmaceutical formulation for treating a GI tract disorder except for acid peptic disorders or structural gastroesophageal disorders adapted for transmucosal drug administration, comprising a therapeutically effective amount of a sodium channel modulator, or a pharmaceutically acceptable salt, ester, amide, prodrug, or active metabolite thereof, and a carrier suitable for transmucosal drug delivery buccally, sublingually, intranasally, rectally, or by inhalation.  
     
     
         38 . A packaged kit for a patient to use in the treatment of a GI tract disorder except for acid peptic disorders or structural gastroesophageal disorders, comprising: a pharmaceutical formulation of a sodium channel modulator; a container housing the pharmaceutical formulation during storage and prior to administration; and instructions for carrying out drug administration in a manner effective to treat a GI tract disorder except for acid peptic disorders or structural gastroesophageal disorders.