COMPOSITIONS OF BUPRENORPHINE AND µ ANTAGONISTS

Abstract

The invention relates to a composition comprising buprenorphine and a μ opioid receptor antagonist, wherein the composition is characterized by an Agonist Antagonist Activity Index (AAnAI) of between about 0.7 and about 2.2; wherein;AAnAI=[Cmax(BUP)/EC50][Cmax(ANTAGONIST)/IC50].

1 - 40 . (canceled) 
     
     
         41 . A method of treating major depressive disorder in a patient in need thereof, comprising administering buprenorphine and Compound-1 or a pharmaceutically acceptable salt thereof to the patient 
       
         
           
           
               
               
           
         
         wherein Compound-1 is administered in a dose of about 0.5 to about 4 mg. 
       
     
     
         42 . The method of  claim 41 , comprising administering the pharmaceutically acceptable salt of Compound-1. 
     
     
         43 . The method according to  claim 41 , wherein buprenorphine and/or Compound-1 or pharmaceutically acceptable salt thereof are administered orally or sublingually. 
     
     
         44 . The method according to  claim 41 , wherein buprenorphine and/or Compound-1 or pharmaceutically acceptable salt thereof are administered daily. 
     
     
         45 . The method according to  claim 41 , wherein buprenorphine and/or Compound-1 or pharmaceutically acceptable salt thereof are in the form of a tablet. 
     
     
         46 . The method according to  claim 41 , wherein buprenorphine and Compound-1 or pharmaceutically acceptable salt thereof are in a pharmaceutical composition. 
     
     
         47 . The method according to  claim 46 , wherein the composition is administered daily. 
     
     
         48 . The method according to  claim 46 , wherein the composition is in the form of a tablet. 
     
     
         49 . The method according to  claim 41 , wherein Compound-1 or a pharmaceutically acceptable salt thereof is administered in a dose of about 2 mg. 
     
     
         50 . The method according to  claim 41 , comprising 2 mg to 4 mg of buprenorphine. 
     
     
         51 . The method according to  claim 41 , comprising 2mg of buprenorphine. 
     
     
         52 . The method according to  claim 41 , wherein said major depressive disorder is resistant to two or more antidepressants. 
     
     
         53 . The method according to  claim 52 , wherein said antidepressants are selected from the group consisting of selective serotonin reuptake inhibitors (SSRIs), Serotonin-norepinephrine reuptake inhibitors (SNRIs), Monoamine oxidase inhibitors (MAOIs) and Tricyclic antidepressants. 
     
     
         54 . The method according to  claim 41 , wherein the method results in the reduction of buprenorphine-induced dopamine release as compared to administration of buprenorphine alone. 
     
     
         55 . The method according to  claim 54 , wherein the method results in a reduction in dopamine release of between about 25% to about 75% in comparison with the administration of buprenorphine alone. 
     
     
         56 . The method according to  claim 41 , wherein the method reduces the drug liking and addictive potential of buprenorphine while retaining the anti-depressive properties of buprenorphine.