Use of derivatives of valproic acid amides and 2-valproenic acid amides for the treatment of prevention of pain and/or headache disorders

Abstract

A method for the treatment or prevention of pain and/or a headache disorder using a derivative of a valproic acid amide or a 2-valproenic acid amide, as well as pharmaceutical compositions comprising these derivatives or compounds.

What is claimed:  
     
         1 . A method of treating a subject suffering from pain comprising periodically administering to the subject a therapeutically effective dose of a compound having the following structure:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3  and R 4  are independently the same or different and are hydrogen, a linear or branched C 1 -C 6  alkyl group, an aralkyl group, or an aryl group, and n is an integer which is greater than or equal to 0 and less than or equal to 3, so as to thereby treat the subject's pain.  
     
     
         2 . The method of  claim 1 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a linear chain C 1 -C 6  alkyl group.  
     
     
         3 . The method of  claim 1 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a branched chain C 1 -C 6  alkyl group.  
     
     
         4 . The method of  claim 1 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a benzyl, alkylbenzyl, hydroxybenzyl, alkoxycarbonylbenzyl, aryloxycarbonylbenzyl, carboxybenzyl, nitrobenzyl, cyanobenzyl, or halobenzyl group.  
     
     
         5 . The method of  claim 1 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a phenyl, naphthyl, anthracenyl, pyridinyl, indolyl, furanyl, alkylphenyl, hydroxyphenyl, alkoxycarbonylphenyl, aryloxycarbonylphenyl, nitrophenyl, cyanophenyl, halophenyl group, mercaptophenyl, or aminophenyl group.  
     
     
         6 . The method of  claim 1 , wherein the pain is acute pain.  
     
     
         7 . The method of  claim 1 , wherein the pain is chronic pain.  
     
     
         8 . The method of  claim 1 , wherein the pain is somatogenic pain.  
     
     
         9 . The method of  claim 8 , wherein the somatogenic pain is neuropathic pain.  
     
     
         10 . The method of  claim 1 , wherein the subject is a human being.  
     
     
         11 . The method of  claim 1 , wherein the administration is oral, parenteral, intraperitoneal, intravenous, intramuscular, transdermal, subcutaneous, topical or rectal administration.  
     
     
         12 . The method of  claim 1 , wherein the administration is by inhalation, sublingual, nasal, buccal, pulmonary or vaginal administration.  
     
     
         13 . The method of  claim 1 , wherein the periodic administration is effected daily.  
     
     
         14 . The method of  claim 1 , wherein the periodic administration is effected less than or equal to six times a day.  
     
     
         15 . The method of  claim 14 , wherein the periodic administration is effected six times a day.  
     
     
         16 . The method of  claim 1 , wherein the therapeutically effective dose is an amount from about 10 mg to about 6,000 mg.  
     
     
         17 . The method of  claim 16 , wherein the therapeutically effective dose is an amount from about 500 mg to about 4,000 mg.  
     
     
         18 . The method of  claim 16 , wherein the therapeutically-effective dose is an amount from about 10 mg to about. 3,000 mg.  
     
     
         19 . The method of  claim 18 , wherein the therapeutically effective dose is about 3,000 mg.  
     
     
         20 . The method of  claim 18 , wherein the therapeutically effective dose is an amount from about 10 mg to about 1,000 mg.  
     
     
         21 . The method of  claim 20 , wherein the therapeutically effective dose is an amount from about 50 mg to about 500 mg.  
     
     
         22 . The method of  claim 1 , wherein the compound has the following structure:  
       
         
           
           
               
               
           
         
       
     
     
         23 . The method of  claim 22 , wherein the compound is N-(2-n-propylpentanoyl)glycinamide.  
     
     
         24 . The method of  claim 23 , wherein the therapeutically effective dose is 3000 mg/day and the pain is neuropathic pain.  
     
     
         25 . The method of  claim 22 , wherein the compound is N-2(-n-propylpent-2-enoyl)glycinamide.  
     
     
         26 . The method of  claim 22 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a linear chain C 1 -C 6  alkyl group.  
     
     
         27 . The method of  claim 22 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a branched chain C 1 -C 6  alkyl group.  
     
     
         28 . The method of  claim 22 , wherein one or more of R 1 , R 2 , R 3  or R 4  is aralkyl group is a benzyl, alkylbenzyl, hydroxybenzyl, alkoxycarbonylbenzyl, aryloxycarbonylbenzyl, carboxybenzyl, nitrobenzyl, cyanobenzyl, or halobenzyl group.  
     
     
         29 . The method of  claim 22 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a phenyl, naphthyl, anthracenyl, pyridinyl, indolyl, furanyl, alkylphenyl, hydroxyphenyl, alkoxycarbonylphenyl, aryloxycarbonylphenyl, nitrophenyl, cyanophenyl, halophenyl group, mercaptophenyl, or aminophenyl group.  
     
     
         30 . The method of  claim 22 , wherein the pain is acute pain.  
     
     
         31 . The method of  claim 22 , wherein the pain is chronic pain.  
     
     
         32 . The method of  claim 22 , wherein the pain is somatogenic pain.  
     
     
         33 . The method of  claim 32 , wherein the somatogenic pain is neuropathic pain.  
     
     
         34 . The method of  claim 22 , wherein the subject is a human being.  
     
     
         35 . The method of  claim 22 , wherein the administration oral, parenteral, intraperitoneal, intravenous, intramuscular, transdermal, subcutaneous, topical or rectal administration.  
     
     
         36 . The method of  claim 22 , wherein the administration is by inhalation, sublingual, nasal, buccal, pulmonary or vaginal administration.  
     
     
         37 . The method of  claim 22 , wherein the periodic administration is effected daily.  
     
     
         38 . The method of  claim 22 , wherein the periodic administration is effected less than or equal to six times a day.  
     
     
         39 . The method of claim. 38, wherein the periodic administration is effected six times a day.  
     
     
         40 . The method of  claim 22 , wherein the therapeutically effective dose is an amount from about 10 mg to about 6,000 mg.  
     
     
         41 . The method of  claim 40 , wherein the therapeutically effective dose is an amount from about 500 mg to about 4,000 mg.  
     
     
         42 . The method of  claim 40 , wherein the therapeutically effective dose is an amount from about 10 mg to about 3,000 mg.  
     
     
         43 . The method of  claim 42 , wherein the therapeutically effective dose is about 3,000 mg.  
     
     
         44 . The method of  claim 42 , wherein the therapeutically effective dose is an amount from about 10 mg to about 1,000 mg.  
     
     
         45 . The method of  claim 44 , wherein the therapeutically effective dose is an amount from about 50 mg to about 500 mg.  
     
     
         46 . A method of treating a subject suffering from neuropathic pain comprising administering to the subject 500 mg of N-(2-n-propylpentanoyl)glycinamide six times per day so as to thereby treat the subject's neuropathic pain.  
     
     
         47 . A method of preventing pain in a subject predisposed to suffering from pain comprising periodically administering to the subject a prophylactically effective dose of a compound having the following structure:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3  and R 4  are independently the same or different and are hydrogen, a linear or branched C 1 -C 6  alkyl group, an aralkyl group, or an aryl group, and n is an integer which is greater than or equal to 0 and less than or equal to 3, so as to thereby prevent pain in the subject.  
     
     
         48 . The method of  claim 47 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a linear chain C 1 -C 6  alkyl group.  
     
     
         49 . The method of  claim 47 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a branched chain C 1 -C 6  alkyl group.  
     
     
         50 . The method of  claim 47 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a benzyl, alkylbenzyl, hydroxybenzyl, alkoxycarbonylbenzyl, aryloxycarbonylbenzyl, carboxybenzyl, nitrobenzyl, cyanobenzyl, or halobenzyl group.  
     
     
         51 . The method of  claim 47 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a phenyl, naphthyl, anthracenyl, pyridinyl, indolyl, furanyl, alkylphenyl, hydroxyphenyl, alkoxycarbonylphenyl, aryloxycarbonylphenyl, nitrophenyl, cyanophenyl, halophenyl group, mercaptophenyl, or aminophenyl group.  
     
     
         52 . The method of  claim 47 , wherein the pain is acute pain.  
     
     
         53 . The method of  claim 47 , wherein the pain is chronic pain.  
     
     
         54 . The method of  claim 47 , wherein the pain is somatogenic pain.  
     
     
         55 . The method of  claim 54 , wherein the somatogenic pain is neuropathic pain.  
     
     
         56 . The method of  claim 47 , wherein the subject is a human being.  
     
     
         57 . The method of  claim 47 , wherein the administration is oral, parenteral, intraperitoneal, intravenous, intramuscular, transdermal, subcutaneous, topical or rectal administration.  
     
     
         58 . The method of  claim 47 , wherein the administration is by inhalation, sublingual, nasal, buccal, pulmonary or vaginal administration.  
     
     
         59 . The method of  claim 47 , wherein the periodic administration is effected daily.  
     
     
         60 . The method of  claim 47 , wherein the periodic administration is effected less than or equal to six times a day.  
     
     
         61 . The method of  claim 60 , wherein the periodic administration is effected six times a day.  
     
     
         62 . The method of  claim 47 , wherein the prophylactically effective dose is an amount from about 10 mg to about 6,000 mg.  
     
     
         63 . The method of  claim 62 , wherein the prophylactically effective dose is an amount from about 500 mg to about 4,000 mg.  
     
     
         64 . The method of  claim 62 , wherein the prophylactically effective dose is an amount from about 10 mg to about 3,000 mg.  
     
     
         65 . The method of  claim 64 , wherein the prophylactically effective dose is about 3,000 mg.  
     
     
         66 . The method of  claim 64 , wherein the prophylactically effective dose is an amount from about 10 mg to about 1,000 mg.  
     
     
         67 . The method of  claim 66 , wherein the prophylactically effective dose is an amount from about 50 mg to about 500 mg.  
     
     
         68 . The method of  claim 47 , wherein the compound the following structure:  
       
         
           
           
               
               
           
         
       
     
     
         69 . The method of  claim 68 , wherein the compound is N-(2-n-propylpentanoyl)glycinamide.  
     
     
         70 . The method of  claim 69 , wherein the prophylactically effective dose is 3000 mg/day and the pain is neuropathic pain.  
     
     
         71 . The method of  claim 68 , wherein the compound is N-2(-n-propylpent-2-enoyl)glycinamide.  
     
     
         72 . The method of  claim 68 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a linear chain C 1 -C 6  alkyl group.  
     
     
         73 . The method of  claim 68 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a branched chain C 1 -C 6  alkyl group.  
     
     
         74 . The method of  claim 68 , wherein one or more of R 1 , R 2 , R 3  or R 4  is aralkyl group is a benzyl, alkylbenzyl, hydroxybenzyl, alkoxycarbonylbenzyl, arylokycarbonylbenzyl, carboxybenzyl, nitrobenzyl, cyanobenzyl, or halobenzyl group.  
     
     
         75 . The method of  claim 68 , wherein one or more of R 1 , R 2 , R 3  or R 4  is a phenyl, naphthyl, anthracenyl, pyridinyl, indolyl, furanyl, alkylphenyl, hydroxyphenyl, alkoxycarbonylphenyl, aryloxycarbonylphenyl, nitrophenyl, cyanophenyl, halophenyl group, mercaptophenyl, or aminophenyl group.  
     
     
         76 . The method of  claim 68 , wherein the pain is acute pain.  
     
     
         77 . The method of  claim 68 , wherein the pain is chronic pain.  
     
     
         78 . The method of  claim 68 , wherein the pain is somatogenic pain.  
     
     
         79 . The method of  claim 78 , wherein the somatogenic pain is neuropathic pain.  
     
     
         80 . The method of  claim 68 , wherein the subject is a human being.  
     
     
         81 . The method of  claim 68 , wherein the administration oral, parenteral, intraperitoneal, intravenous, intramuscular, transdermal, subcutaneous, topical or rectal administration.  
     
     
         82 . The method of  claim 68 , wherein the administration is by inhalation, sublingual, nasal, buccal, pulmonary or vaginal administration.  
     
     
         83 . The method of  claim 68 , wherein the periodic administration is effected daily.  
     
     
         84 . The method of  claim 68 , wherein the periodic administration is effected less than or equal to six times a day.  
     
     
         85 . The method of  claim 68 , wherein the periodic administration is effected six times a day.  
     
     
         86 . The method of  claim 68 , wherein the prophylactically effective dose is an amount from about 10 mg to about 6,000 mg.  
     
     
         87 . The method of  claim 86 , wherein the prophylactically effective dose is an amount from about 500 mg to about 4,000 mg.  
     
     
         88 . The method of  claim 86 , wherein the prophylactically effective dose is an amount from about 10 mg to about 3,000 mg.  
     
     
         89 . The method of  claim 88 , wherein the prophylactically effective dose is about 3,000 mg.  
     
     
         90 . The method of  claim 88 , wherein the prophylactically effective dose is an amount from about 10 mg to about 1,000 mg.  
     
     
         91 . The method of  claim 90 , wherein the prophylactically effective dose is an amount from about 50 mg to about 500 mg.  
     
     
         92 . A method of preventing neuropathic pain in a subject predisposed to suffering from neuropathic pain comprising administering to the subject 500 mg of N-(2-n-propylpentanoyl)glycinamide six times per day so as to thereby prevent the neuropathic pain in the subject.  
     
     
         93 . A method of treating a subject suffering from pain comprising periodically administering to the subject a pharmaceutical composition comprising a therapeutically effective dose a compound having the following structure:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3  and R 4  are independently the same or different and are hydrogen, a linear or branched C 1 -C 6  alkyl group, an aralkyl group, or an aryl group, and n is an integer which is greater than or equal to 0 and less than or equal to 3, and a pharmaceutically acceptable carrier, so as to thereby treat the subject's pain.  
     
     
         94 . A method of preventing pain in a subject predisposed to suffering from pain comprising periodically administering to the subject a composition comprising a prophylactically effective dose of a compound having the following structure:  
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3  and R 4  are independently the same or different and are hydrogen, a linear or branched C 1 -C 6  alkyl group, an aralkyl group, or an aryl group, and n is an integer which is greater than or equal to 0 and less than or equal to 3, and a pharmaceutically acceptable carrier, so as to thereby prevent pain in the subject.  
       
     
     
         95 . A method of treating a subject suffering from a headache disorder comprising periodically administering to the subject a therapeutically effective dose of a compound having the following structure:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3  and R 4  are independently the same or different and are hydrogen, a linear or branched C 1 -C 6  alkyl group, an aralkyl group, or an aryl group, and n is an integer which is greater than or equal to 0 and less than or equal to 3, so as to thereby treat the headache disorder.  
     
     
         96 . A method of preventing a headache disorder in a subject predisposed to suffering from a headache disorder comprising periodically administering to the subject a prophylactically effective dose of a compound having the following structure:  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3  and R 4  are independently the same or different and are hydrogen, a linear or branched C 1 -C 6  alkyl group, an aralkyl group, or an aryl group, and n is an integer which is greater than or equal to 0.0 and less than or equal to 3, so as to thereby prevent the headache disorder in the subject.