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 of treating a subject with attention deficit disorder; a learning disability; obesity; Alzheimer's disease; amnesia; a memory disorder or impairment; fibromyalgia; fatigue; chronic fatigue; depression; epilepsy; obsessive compulsive disorder; oppositional defiant disorder; anxiety; resistant depression; stroke rehabilitation; Parkinson's disease; mood disorder; schizophrenia; Huntington's disorder; dementia; movement dysfunction; apathy; Pick's disease; Creutzfeldt-Jakob disease; a sleep disorder; a condition related to brain injury or neuronal degeneration; Tourette's syndrome; impotence; or nicotine dependence or withdrawal; said method comprising orally administering to said subject in need thereof, a therapeutically effective amount of L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof. 
     
     
         2 . A method as defined in  claim 1 , wherein said L-lysine-d-amphetamine or a pharmaceutically acceptable salt thereof is in a dosage form selected from the group consisting of a tablet, a capsule, a caplet, an oral solution, or an oral suspension. 
     
     
         3 . A method as defined in  claim 1 , wherein said L-lysine-d-amphetamine is in the form of a salt. 
     
     
         4 . A method as defined in  claim 3 , wherein said salt is a mesylate salt. 
     
     
         5 . A method as defined in  claim 4 , wherein said salt is a dimesylate salt. 
     
     
         6 . A method as defined in  claim 3 , wherein said salt is a hydrochloride salt. 
     
     
         7 . A method as defined in  claim 1 , wherein said therapeutically effective amount is an amount sufficient to provide a therapeutically bioequivalent AUC when compared to amphetamine alone, but which does not provide a C max  which results in euphoria. 
     
     
         8 . A method as defined in  claim 2 , wherein said therapeutically effective amount in said dosage form is from about 5 mg to about 500 mg of said L-lysine-d-amphetamine or a salt thereof. 
     
     
         9 . A method as defined in  claim 8  wherein said therapeutically effective amount in said dosage form is said L-lysine-d-amphetamine or a salt thereof. 
     
     
         10 . A method as defined in  claim 2 , wherein said dosage form is administered one or more times per 24-hour period. 
     
     
         11 . A method as defined in  claim 8  wherein said dosage form is administered one or more times per 24-hour period. 
     
     
         12 . A method as defined in  claim 9 , wherein said dosage form is administered one or more times per 24-hour period.