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 composition having the formula:
   A-X n -Z m      wherein A is an amphetamine;   each X is the same or different amino acid;   each Z is the same or different chemical moiety that is an adjuvant for A;   n is an integer from 1 to 10; and   m is an integer from 1 to 50;   
     or a salt thereof. 
   
   
       2 . A composition 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. 
   
   
       3 . A composition as defined in  claim 1 , wherein Z is selected from the group consisting of carbohydrates, lipids, nucleosides, nucleic acids, and vitamins. 
   
   
       4 . A composition as defined in  claim 1 , wherein said composition is in a dosage form selected from the group consisting of a tablet, capsule, caplet, oral solution, and oral suspension. 
   
   
       5 . A composition as defined in  claim 4 , wherein said dosage form further comprises 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. 
   
   
       6 . A composition having the formula:
   A-X n -Z m      wherein A is an amphetamine;   each X is the same or different amino acid;   each Z is the same or different chemical moiety that is an adjuvant for A;   n is an integer from 1 to 10; and   m is an integer from 1 to 50;   
     or a salt thereof; 
     wherein said composition provides a therapeutically bioequivalent AUC of said amphetamine when compared to the AUC of said amphetamine when administered in a form in which said amphetamine is not covalently bonded to X n -Z m . 
   
   
       7 . A method, in a subject in need thereof, of treating attention deficit hyperactivity disorder, said method comprising administering to said subject a composition as defined in  claim 1  or  6 .