Methods for treating migraines with huperzine a derivatives

Abstract

The present invention relates to a method for treating, alleviating, or preventing pain, particularly migraines, functional pain syndrome, or organic pain syndrome, by administering to a patient in need thereof compound (I), or salts thereof, or pharmaceutical preparations thereof comprising mixtures of compound (I) or salts thereof with pharmaceutically-acceptable diluents wherein: R represents —NR 1 R 2 , —NHC(O)OR 3 , or —N═CR 4 R 5 ; R 1 represents H, or a C 1-6 alkyl; R 2 represents H, or a C 1-6 alkyl; R 3 represents a C 1-6 alkyl, a heterocyclic group, or an aryl; R 4 represents H, C 1-6 alkyl, a heterocyclic group or an aryl; and R 5 represents H, C 1-6 alkyl, a heterocyclic group, or an aryl; or CR 4 R 5 taken together represents a cyclolidene group.

1 . A method for treating or alleviating migraines comprising administering to a patient in need thereof a compound of the formula (I), or its salt, 
       
         
           
           
               
               
           
         
       
       wherein
 R represents —NR 1 R 2 ; 
 R 1  represents H, or a C 1-6  alkyl; and 
 R 2  represents H, or a C 1-6  alkyl; 
 
     
     
         2 . The method of  claim 1 , wherein
 R represents —NR 1 R 2 ; and   R 1  and R 2  represent independently and at each occurrence hydrogen or a C 1-3  alkyl.   
     
     
         3 . The method of  claim 1 , wherein
 R represents —NR 1 R 2 ; and   R 1  and R 2  represent independently and at each occurrence hydrogen, methyl, or ethyl.   
     
     
         4 . The method of  claim 1 , wherein the compound of the general formula (I), or its salt is administered to the patient by a mode of administration selected from gastrointestinal, oral, intravenous, abdominal, dermal, intramuscular, nasal, ocular, pulmonary, anal, vaginal, or transdermal. 
     
     
         5 . The method of  claim 1 , wherein the compound of the general formula (I), or its salt is administered to the patient at a dose of between 10 μg and 100 mg. 
     
     
         6 . A method for treating or alleviating migraines comprising administering to a patient in need thereof a compound of formula (I), or its salt, 
       
         
           
           
               
               
           
         
       
       wherein
 R represents —NR 1 R 2 ; 
 R 1  represents H, or a C 1-6  alkyl; 
 R 2  represents H, or a C 1-6  alkyl; and 
 except that R 1  and R 2  are not simultaneously H. 
 
     
     
         7 . A method for treating or alleviating migraines comprising administering to a patient in need thereof a compound of the formula (I), or its salt, 
       
         
           
           
               
               
           
         
       
       wherein
 R represents —NHC(O)OR 3 , or —N═CR 4 R 5 ; 
 R 3  represents a C 1-6  alkyl, a heterocyclic group, or an aryl; and 
 R 4  and R 5  represent independently a C 1-6  alkyl, a heterocyclic group, or an aryl; or CR 4 R 5  taken together represents a cyclolidene group. 
 
     
     
         8 . The method of  claim 7 , wherein
 R represents —N═CR 4 R 5 ; and   CR 4 R 5  represent cyclopentylidene, cyclohexylidene, or 1-methyl-4-piperidinylidene.   
     
     
         9 . The method of  claim 7 , wherein
 R represents —N═CR 4 R 5 ; and   R 4  and R 5  represent, independently and at each occurrence, hydrogen, a C 1-3  alkyl, a phenyl, a substituted phenyl, a 2-pyrrolinyl, a 3-pyridinyl, or a 4-pyridinyl.   
     
     
         10 . The method of  claim 7 , wherein the compound of the general formula (I), or its salt is administered to the patient by a mode of administration selected from gastrointestinal, oral, intravenous, abdominal, dermal, intramuscular, nasal, ocular, pulmonary, anal, vaginal, or transdermal. 
     
     
         11 . The method of  claim 7 , wherein the compound of the general formula (I), or its salt is administered to the patient at a dose of between 10 μg and 100 mg. 
     
     
         12 . The method of  claim 7 , wherein said compound of formula (I) is (5R,9R,11E)-5-(2-methylpropoxycarbonylamino)-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[b]pyridin-2(1H)-one. 
     
     
         13 . The method of  claim 7 , wherein said compound of formula (I) is (5R,9R,11E)-5-(4-hydroxy-3-methoxyphenylmethylidenylamino)-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[b]pyridin-2(1H)-one.