Methods of treating prader-willi syndrome

Abstract

Methods of treating Prader-Willi syndrome in a subject in need of treatment are provided. The methods include administering to the subject an effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein R, R′, X, Y and Z are defined as set forth in the specification. In embodiments, an effective amount of captodiamine or a pharmaceutically acceptable salt thereof is administered to the subject.

What is claimed is: 
     
         1 . A method of treating Prader-Willi syndrome comprising administering to a subject with Prader-Willi syndrome a pharmaceutical composition comprising an effective amount of a compound according to Formula I 
       
         
           
           
               
               
           
         
       
       wherein X is an ethylene, propylene, butylene or pentylene group; R is C 1-9  alkyl, preferably C 1-5  alkyl; R′ is C 1-9  alkyl, alkenyl or alkynyl; Y is hydrogen, halide, hydroxyC 1-4  alkyl, amino, C 1-4 alkylamino, acetylamino or thio; and Z is hydrogen, halide such as chloro, fluoro, iodo or bromo, hydroxyC 1-4  alkyl, amino, C 1-4  alkylamino, acetylamino or thio, or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The method of treating Prader-Willi syndrome according to  claim 1  wherein X is an ethylene, propylene, butylene, or pentylene group; R is methyl, R′ is butyl, Y is hydrogen and Z is hydrogen; or R is C 1-9  alkyl, C 1-5  alkyl, and R′ is butyl, X is ethylene, Y is hydrogen and Z is hydrogen. 
     
     
         3 . The method of treating Prader-Willi syndrome according to  claim 1  wherein Y is hydrogen, halide such as chloro, fluoro, iodo or bromo, hydroxyl C 1-4 alkyl, amino, C 1-4  alkylamino, acetylamino, or thio, and R is methyl, R′ is butyl, X is ethylene and Z is hydrogen. 
     
     
         4 . The method of treating Prader-Willi syndrome according to  claim 1  wherein R′ is C 1-9  alkyl, alkenyl or alkynyl, R is methyl, X is ethylene, Y is hydrogen and Z is hydrogen. 
     
     
         5 . The method of treating Prader-Willi syndrome according to  claim 1  wherein the compound is captodiamine or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The method of treating Prader-Willi syndrome according to  claim 1  wherein the compound is administered in an amount of 0.01 mg to 1500 mg. 
     
     
         7 . The method of treating Prader-Willi syndrome according to  claim 1  wherein captodiamine or pharmaceutically acceptable salt thereof is administered in an amount of 0.01 mg to 1500 mg. 
     
     
         8 . The method of treating Prader-Willi syndrome according to  claim 1 , wherein the composition provides improvement in at least one symptom selected from the group consisting of hypotonia, difficulty in sucking, difficulty in feeding, poor muscle tone, growth hormone deficiency, low levels of sex hormones, a constant feeling of hunger, excessive appetite (hyperphagia), weight gain, obesity, short stature, poor motor skills, underdeveloped sex organs, intellectual disability, learning disability, delayed speech development, delayed language development, infertility, cognitive rigidity, cognitive impairment, emotional lability, obsessive-compulsive behavior, autistic symptomology, psychotic episodes, bipolar disorder with psychosis, excessive daytime sleepiness, scoliosis, osteopenia/osteoporosis, decreased gastrointestinal motility, sleep disturbances, and reduced pain sensitivity. 
     
     
         9 . The method of treating Prader-Willi syndrome according to  claim 1 , wherein the composition includes pharmaceutically acceptable adjuvants, diluents and/or carriers. 
     
     
         10 . The method of treating Prader-Willi syndrome according to  claim 1 , wherein administering the composition is accomplished via a route selected from the group consisting of oral, buccal, sublingual, rectal, topical, intranasal, and parenteral. 
     
     
         11 . A method of treating Prader-Willi syndrome comprising administering to a subject with Prader-Willi syndrome a pharmaceutical composition comprising an effective amount of captodiamine or a pharmaceutically acceptable salt thereof in an amount of from 0.01 mg to 1500 mg. 
     
     
         12 . The method of treating Prader-Willi syndrome according to  claim 11 , wherein the subject is administered 1 mg to 500 mg of captodiamine or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of treating Prader-Willi syndrome according to  claim 11 , wherein the subject is administered 50 mg to 250 mg of captodiamine or a pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of treating Prader-Willi syndrome according to  claim 11 , wherein the total amount of captodiamine or a pharmaceutically acceptable salt thereof administered to the subject in a twenty-four hour period is between 1 mg and 1500 mg. 
     
     
         15 . The method of treating Prader-Willi syndrome according to  claim 11 , wherein the total amount of captodiamine or a pharmaceutically acceptable salt thereof administered to the subject in a twenty-four hour period is between 1 mg and 500 mg. 
     
     
         16 . The method of treating Prader-Willi syndrome according to  claim 11 , wherein captodiamine or a pharmaceutically acceptable salt thereof is administered from one to four times a day. 
     
     
         17 . The method of treating Prader-Willi syndrome according to  claim 11 , wherein administering the composition is accomplished via a route selected from the group consisting of oral, buccal, sublingual, rectal, topical, intranasal, vaginal and parenteral. 
     
     
         18 . The method of treating Prader-Willi syndrome according to  claim 11 , wherein the composition provides improvement in at least one symptom selected from the group consisting of hypotonia, difficulty in sucking, difficulty in feeding, poor muscle tone, growth hormone deficiency, low levels of sex hormones, a constant feeling of hunger, excessive appetite (hyperphagia), weight gain, obesity, short stature, poor motor skills, underdeveloped sex organs, cognitive impairment, intellectual disability, learning disability, delayed speech development, delayed language development, infertility, cognitive rigidity, emotional lability, self-injury, obsessive-compulsive behavior, autistic symptomology, psychotic episodes, bipolar disorder with psychosis, excessive daytime sleepiness, scoliosis, osteopenia/osteoporosis, decreased gastrointestinal motility, sleep disturbances, and reduced pain sensitivity.