Dopamine analog amide

Abstract

The invention involves the formation of a prodrug from a fatty acid carrier and a neuroactive drug. The prodrug is stable in the environment of both the stomach and the bloodstream and may be delivered by ingestion. The prodrug passes readily through the blood brain barrier. Once in the central nervous system, the prodrug is hydrolyzed into the fatty acid carrier and the drug to release the drug. In a preferred embodiment, the carrier is 4, 7, 10, 13, 16, 19 docosahexa-enoic acid and the drug is dopamine. Both are normal components of the central nervous system. The covalent bond between the drug and the carrier preferably is an amide bond, which bond may survive the conditions in the stomach. Thus, the prodrug may be ingested and will not be hydrolyzed completely into the carrier molecule and drug molecule in the stomach.

What is claimed is:  
     
         1 . A prodrug compound capable of facilitating the passage of a drug across the blood brain barrier comprising: 
 a fatty acid coupled to a nondoparmine drug which is an anti-aids substance, anti-cancer substance, antibiotic, drug affecting adenosine concentrations, adrenergic agent, cholinergic agent, benzodiazepine, drug effecting cocaine receptors, enzyme inhibitor, excitatory amino acid, neuroactive amino acid, GABA-ergic agent, histaminergic agent, ion channel modulator, neurotoxin, opioid, drug affecting PCP/Sigma receptors, serotonergic agent, hypnotic agent, psychic energizer, tranquilizer, anti-convulsant, muscle relaxant, anti-hypertensive agent, analgesic, anti-pyretic agent, anti-inflammatory agent, local anesthetic, muscle contractant, prostaglandin, anti-bacterial agent, anti-septic agent, anti-depressant, anti-migraine preparation, imaging agent, specific targeting agent, protein, peptide, anti-viral agent, anti-psychotic agent, anti-addiction agent, or anti-emetic agent.    
     
     
         2 . A prodrug compound capable of facilitating the passage of a drug across the blood brain barrier comprising a fatty acid carrier molecule coupled to a drug, said fatty acid carrier molecule being selected from the group consisting of C16:0; C16:1; C16:2; C20:1; C20:2; C20:3; C20:4; C22:4; C22:5; C22:6, and C24:4.  
     
     
         3 . A prodrug compound as claimed in  claim 2  selected from the group consisting of  
       
         
           
           
               
               
           
         
       
       wherein D is a neuroactive drug.  
     
     
         4 . A prodrug as claimed in  claim 3  comprising:  
       
         
           
           
               
               
           
         
       
       wherein D is a neuroactive drug.  
     
     
         5 . A prodrug compound as claimed in  claim 2 ,  3 , or  4  wherein the drug is a neurotransmitter.  
     
     
         6 . A prodrug compound as claimed in  claim 2 ,  3 , or  4  wherein the drug is a anorectic compound.  
     
     
         7 . A prodrug compound as claimed in  claim 1 ,  2 ,  3 , or  4  wherein the drug is an anti-aids substance.  
     
     
         8 . A prodrug compound as claimed in  claim 1 ,  2 ,  3 , or  4  wherein the drug is an anti-cancer substance.  
     
     
         9 . A prodrug compound as claimed in  claim 1 ,  2 ,  3 , or  4  wherein the drug is an antibiotic.  
     
     
         10 . A prodrug compound as claimed in  claim 2 ,  3 , or  4  wherein the drug is a dopaminergic agent.  
     
     
         11 . A prodrug compound as claimed in  claim 1 ,  2 ,  3 , or  4  wherein the drug is a protein.  
     
     
         12 . A prodrug compound as claimed in  claim 1 ,  2 ,  3 , or  4  wherein the drug is a peptide.  
     
     
         13 . A prodrug compound as claimed in  claim 1 ,  2 ,  3 , or  4  wherein the drug is an anti-viral agent.  
     
     
         14 . A prodrug compound as claimed in  claim 1  or  2  wherein the fatty acid carrier occurs naturally in the brain.  
     
     
         15 . A prodrug compound as claimed in  claim 1  or  2  wherein the fatty acid carrier is one that occurs naturally in the brain and further having methyl, ethyl or isopropyl group substitutions along the carbon chain.  
     
     
         16 . A prodrug capable of facilitating a passage of a drug across the blood brain barrier comprising: 
 a fatty acid coupled to a drug, provided that when the fatty acid is C:18, the drug is not dopamine.    
     
     
         17 . A pharmaceutical preparation containing the prodrug compound of  claim 1 ,  2  or  16  and a pharmaceutically acceptable carrier.  
     
     
         18 . A pharmaceutical preparation for use in treating an animal comprising, 
 a prodrug having a fatty acid coupled to a drug, and    a pharmaceutically acceptable carrier.    
     
     
         19 . A pharmaceutical preparation as claimed in  claim 18  wherein the carrier is a medium capable of surviving the environment of the stomach.  
     
     
         20 . A pharmaceutical preparation comprising: 
 a pharmaceutically effective amount of a prodrug compound; and    a pharmaceutically acceptable carrier, wherein the prodrug compound comprises a fatty acid coupled to a drug provided that when the fatty acid is C:18, the drug is not dopamine.    
     
     
         21 . A method for introducing a drug into the central nervous system comprising, 
 introducing a pharmaceutically effective amount of a prodrug comprising a fatty acid coupled to a drug into the blood stream of a patient.    
     
     
         22 . A method of manufacturing a pharmaceutical preparation comprising: 
 coupling a fatty acid to a drug thereby forming a prodrug; and    forming a pharmaceutical dose containing the prodrug and a pharmaceutically acceptable carrier.