Compositions for affecting weight loss

Abstract

Disclosed are compositions for affecting weight loss comprising a first compound and a second compound, where the first compound is an opioid antagonist and the second compound causes increased agonism of a melanocortin 3 receptor (MC3-R) or a melanocortin 4 receptor (MC4-R) compared to normal physiological conditions. Also disclosed are methods of affecting weight loss, increasing energy expenditure, increasing satiety in an individual, or suppressing the appetite of an individual, comprising identifying an individual in need thereof and treating that individual to antagonize opioid receptor activity and to enhance α-MSH activity.

1 . A composition for affecting weight loss comprising a first compound and a second compound, wherein said first compound is μ-opioid antagonist and said second compound is selected from the group consisting of a dopamine reuptake inhibitor, a norepinephrine reuptake inhibitor, a mixed dopamine/norepinephrine reuptake inhibitor, a dopamine agonist, a norepinephrine agonist, and a norepinephrine releaser.  
   
   
       2 . The composition of  claim 1 , wherein said μ-opioid antagonist is selected from the group consisting of alvimopan, nalmefene, naloxone, naltrexone, methylnaltrexone, nalorphine, and pharmaceutically acceptable salts thereof.  
   
   
       3 . The composition of  claim 2 , wherein said first compound is naltrexone or pharmaceutically acceptable salt thereof.  
   
   
       4 . The composition of  claim 3 , wherein said second compound is a norepinephrine reuptake inhibitor.  
   
   
       5 . The composition of  claim 4 , wherein said second compound is selected from the group consisting of bupropion, thionisoxetine, reboxetine, and pharmaceutically acceptable salts thereof  
   
   
       6 . The composition of  claim 1 , wherein said second compound is a norepinephrine reuptake inhibitor.  
   
   
       7 . The composition of  claim 6 , wherein said second compound is selected from the group consisting of bupropion, thionisoxetine, reboxetine, and pharmaceutically acceptable salts thereof.  
   
   
       8 . The composition of  claim 2 , wherein said second compound is selected from the group consisting of bupropion, thionisoxetine, reboxetine, and pharmaceutically acceptable salts thereof.  
   
   
       9 . The composition of  claim 1 , wherein said first compound is naltrexone or pharmaceutically acceptable salt thereof, and said second compound is bupropion or pharmaceutically acceptable salt thereof.  
   
   
       10 . The composition of  claim 9 , wherein said composition is a sustained release composition.  
   
   
       11 . The composition of  claim 9 , wherein said second compound is sustained release bupropion.  
   
   
       12 . A pharmaceutical composition for affecting weight loss comprising a first compound, a second compound, and a carrier or excipient, wherein said first compound is a μ-opioid antagonist and said second compound is selected from the group consisting of a dopamine reuptake inhibitor, a norepinephrine reuptake inhibitor, a mixed dopamine/norepinephrine reuptake inhibitor, a dopamine agonist, a norepinephrine agonist, and a norepinephrine releaser.  
   
   
       13 . The pharmaceutical composition of  claim 12 , wherein said μ-opioid antagonist is selected from the group consisting of alvimopan, nalmefene, naloxone, naltrexone, methylnaltrexone, nalorphine, and pharmaceutically acceptable salts thereof.  
   
   
       14 . The pharmaceutical composition of  claim 13 , wherein said first compound is naltrexone or pharmaceutically acceptable salt thereof.  
   
   
       15 . The pharmaceutical composition of  claim 14 , wherein said second compound is a norepinephrine reuptake inhibitor.  
   
   
       16 . The pharmaceutical composition of  claim 15 , wherein said second compound is selected from the group consisting of bupropion, thionisoxetine, reboxetine, and pharmaceutically acceptable salts thereof  
   
   
       17 . The pharmaceutical composition of  claim 12 , wherein said second compound is a norepinephrine reuptake inhibitor.  
   
   
       18 . The pharmaceutical composition of  claim 17 , wherein said second compound is selected from the group consisting of bupropion, thionisoxetine, reboxetine, and pharmaceutically acceptable salts thereof.  
   
   
       19 . The pharmaceutical composition of  claim 13 , wherein said second compound is selected from the group consisting of bupropion, thionisoxetine, reboxetine, and pharmaceutically acceptable salts thereof.  
   
   
       20 . The pharmaceutical composition of  claim 12 , wherein said first compound is naltrexone or pharmaceutically acceptable salt thereof, and said second compound is bupropion or pharmaceutically acceptable salt thereof.  
   
   
       21 . The pharmaceutical composition of  claim 20 , wherein said composition is a sustained release composition.  
   
   
       22 . The pharmaceutical composition of  claim 20 , wherein said second compound is sustained release bupropion.  
   
   
       23 . A method of affecting weight loss, comprising identifying an individual in need thereof and administering to said individual the pharmaceutical composition of  claim 12 .  
   
   
       24 . The method of  claim 23 , wherein said μ-opioid antagonist is selected from the group consisting of alvimopan, nalmefene, naloxone, naltrexone, methylnaltrexone, nalorphine, and pharmaceutically acceptable salts thereof, and said second compound is selected from the group consisting of bupropion, thionisoxetine, reboxetine, and pharmaceutically acceptable salts thereof.  
   
   
       25 . The method of  claim 23 , wherein said first compound is naltrexone or pharmaceutically acceptable salt thereof, and said second compound is bupropion or pharmaceutically acceptable salt thereof.  
   
   
       26 . The method of  claim 25 , wherein said second compound is sustained release bupropion.  
   
   
       27 . A method of affecting weight loss, comprising identifying an individual in need thereof and administering to said individual a first compound and a second compound, wherein said first compound is an opioid antagonist and said second compound is selected from the group consisting of a dopamine reuptake inhibitor, a norepinephrine reuptake inhibitor, a mixed dopamine/norepinephrine reuptake inhibitor, a dopamine agonist, norepinephrine agonist, a norepinephrine releaser, a SSRI, a combination of a dopamine reuptake inhibitor and a norepinephrine reuptake inhibitor, and a combination of a SSRI and a norepinephrine reuptake inhibitor.  
   
   
       28 . The method of  claim 27 , wherein said second compound is a norepinephrine reuptake inhibitor or a SSRI.  
   
   
       29 . The method of  claim 28 , wherein said second compound is selected from the group consisting of fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, escitalopram, sibutramine, duloxetine, venlafaxine, bupropion, thionisoxetine, and reboxetine, and pharmaceutically acceptable salts thereof.  
   
   
       30 . The method of  claim 27 , wherein said first compound is selected from the group consisting of alvimopan, nalmefene, naloxone, naltrexone, methylnaltrexone, nalorphine, and pharmaceutically acceptable salts thereof.  
   
   
       31 . The method of  claim 27 , wherein said first compound is naltrexone or a pharmaceutically acceptable salt thereof, and said second compound is bupropion or fluoxetine, or a pharmaceutically acceptable salt thereof.  
   
   
       32 . The method of  claim 31 , wherein at least one of said first compound and said second compound is in a sustained release form.  
   
   
       33 . The method of  claim 31 , wherein said first compound and said second compound are administered in a single unit dosage form.  
   
   
       34 . The method of  claim 33 , unit dosage form is in a sustained release form.  
   
   
       35 . The method of  claim 31 , wherein said first compound and said second compound are administered nearly simultaneously.  
   
   
       36 . The method of  claim 31 , wherein the first compound is administered prior to the second compound.  
   
   
       37 . The method of  claim 31 , wherein the first compound is administered subsequent to the second compound.