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 an opioid antagonist and said second compound causes increased agonism of a melanocortin 3 receptor (MC3-R) or a melanocortin 4 receptor (MC4-R) compared to normal physiological conditions.  
   
   
       2 . The composition of  claim 1 , wherein said opioid antagonist antagonizes an opioid receptor selected from a μ-opioid receptor (MOP-R), a κ-opioid receptor, and a δ-opioid receptor.  
   
   
       3 . The composition of  claim 1 , wherein said opioid antagonist is selected from the group consisting of alvimopan, norbinaltorphimine, nalmefene, naloxone, naltrexone, methylnaltrexone, and nalorphine, and pharmaceutically acceptable salts or prodrugs thereof.  
   
   
       4 . The composition of  claim 1 , wherein said second compound triggers the release of α-melanocyte stimulating hormone (α-MSH).  
   
   
       5 . The composition of  claim 4 , wherein said second compound increases the extracellular serotonin concentrations in the hypothalamus.  
   
   
       6 . The composition of  claim 5 , wherein said second compound is selected from the group consisting of a selective serotonin reuptake inhibitor (SSR), a serotonin 2C agonist, and a serotonin 1B agonist.  
   
   
       7 . The composition of  claim 6 , wherein said second compound is selected from the group consisting of fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, escitalopram, sibutramine, duloxetine, and venlafaxine, and pharmaceutically acceptable salts or prodrugs thereof.  
   
   
       8 . The composition of  claim 1 , wherein said first compound is naltrexone and said second compound is fluoxetine.  
   
   
       9 . The composition of  claim 1 , wherein said first compound is naltrexone and said second compound is bupropion.  
   
   
       10 . The composition of  claim 9 , wherein said first compound is naltrexone and said second compound is sustained release bupropion.  
   
   
       11 . A method of affecting weight loss, comprising identifying an individual in need thereof, and administering to said individual a first compound to antagonize opioid receptor activity and a second compound to enhance α-MSH activity.  
   
   
       12 . The method of  claim 11 , wherein said individual has a body mass index greater than 25.  
   
   
       13 . The method of  claim 11 , wherein said first compound is an opioid receptor antagonist.  
   
   
       14 . The method of  claim 13 , wherein the opioid receptor antagonist is a MOP receptor antagonist.  
   
   
       15 . The method of  claim 11 , wherein the opioid receptor antagonist is selected from alvimopan, norbinaltorphimine, nalmefene, naloxone, naltrexone, methylnaltrexone, and nalorphine, and pharmaceutically acceptable salts or prodrugs thereof.  
   
   
       16 . The method of  claim 11 , wherein said second compound triggers the release of α-MSH or increases the activity of neurons that express α-MSH.  
   
   
       17 . The method of  claim 16 , wherein said second compound is a SSRI or a specific 5-HT receptor agonist.  
   
   
       18 . The method of  claim 17 , wherein said SSRI is selected from fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, escitalopram, sibutramine, duloxetine, and venlafaxine, and pharmaceutically acceptable salts or prodrugs thereof.  
   
   
       19 . The method of  claim 11 , wherein said first compound and said second compound are administered nearly simultaneously.  
   
   
       20 . The method of  claim 11 , wherein said individual does not suffer from depression, Prader-Willi syndrome, or binge eating disorder.  
   
   
       21 . The method of  claim 11 , wherein said first compound is naltrexone and said second compound is bupropion.  
   
   
       22 . The method of  claim 21 , wherein said first compound is naltrexone and said second compound is sustained release bupropion.