Abuse-resistant amphetamine prodrugs

Abstract

The invention describes compounds, compositions, and methods of using the same comprising a chemical moiety covalently attached to amphetamine. These compounds and compositions are useful for reducing or preventing abuse and overdose of amphetamine. These compounds and compositions find particular use in providing an abuse-resistant alternative treatment for certain disorders, such as attention deficit hyperactivity disorder (ADHD), ADD, narcolepsy, and obesity. Oral bioavailability of amphetamine is maintained at therapeutically useful doses. At higher doses bioavailability is substantially reduced, thereby providing a method of reducing oral abuse liability. Further, compounds and compositions of the invention decrease the bioavailability of amphetamine by parenteral routes, such as intravenous or intranasal administration, further limiting their abuse liability.

1 . A method, in a subject in need thereof, of preventing stimulation due to an amphetamine, said method comprising administering to said subject a prodrug or a salt thereof, said prodrug comprising said amphetamine covalently bonded to a single amino acid or to a peptide comprising from 2 to 10 amino acids. 
     
     
         2 . A method as defined in  claim 1 , wherein said subject is an adult human. 
     
     
         3 . A method as defined in  claim 1 , wherein said subject is a human who is not an adult. 
     
     
         4 . A method as defined in  claim 1 , wherein said administration is by the oral route. 
     
     
         5 . A method as defined in  claim 1 , wherein said amphetamine is selected from the group consisting of methylphenidate, methamphetamine, a compound having the formula 
       
         
           
           
               
               
           
         
       
       a salt of any of the foregoing, or a combination of any of the foregoing. 
     
     
         6 . A method as defined in  claim 1 , wherein the amount of said prodrug is from 10 to 100 mg. 
     
     
         7 . A method as defined in  claim 1 , further comprising administering to said subject a pharmacological substance selected from the group consisting of amphetamines, antidepressants, anxiolytics, non-steroidal anti-inflammatory drugs, or any combination of any of the foregoing. 
     
     
         8 . A method as defined in  claim 1 , wherein said subject suffers from attention deficit hyperactivity disorder. 
     
     
         9 . A method, in a subject in need thereof, of diminishing stimulation due to an amphetamine, said method comprising administering to said subject a prodrug or a salt thereof, said prodrug comprising said amphetamine covalently bonded to a single amino acid or to a peptide comprising from 2 to 10 amino acids. 
     
     
         10 . A method as defined in  claim 9 , wherein said subject is an adult human. 
     
     
         11 . A method as defined in  claim 9 , wherein said subject is a human who is not an adult. 
     
     
         12 . A method as defined in  claim 9 , wherein said administration is by the oral route. 
     
     
         13 . A method as defined in  claim 9 , wherein said amphetamine is selected from the group consisting of methylphenidate, methamphetamine, a compound having the formula 
       
         
           
           
               
               
           
         
       
       a salt of any of the foregoing, or a combination of any of the foregoing. 
     
     
         14 . A method as defined in  claim 9 , wherein the amount of said prodrug is from 10 to 100 mg. 
     
     
         15 . A method as defined in  claim 9 , further comprising administering to said subject a pharmacological substance selected from the group consisting of amphetamines, antidepressants, anxiolytics, non-steroidal anti-inflammatory drugs, or any combination of any of the foregoing. 
     
     
         16 . A method as defined in  claim 9 , wherein said subject suffers from attention deficit hyperactivity disorder.