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US 2003/0216458 A1Published application
Combination therapy for the treatment of migraine
OwnerWilma M. Harrison, George H. Sandsinventors
Life of this patent
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Abstract
The present invention relates to a method of treating migraine in a mammal, including a human, by administering to the mammal a 5HT1 receptor agonist in combination with caffeine and a cyclooxygenase-2 (COX-2) inhibitor. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a 5HT1 receptor agonist with caffeine a cyclooxygenase-2 (COX-2) inhibitor.
Claims10
A pharmaceutical composition for the treatment of migraine comprising a 5HT1 receptor agonist or a pharmaceutically acceptable salt thereof, and caffeine, with (a) a compound of the formula
- 6
- wherein R1 is sulfamyl;
- wherein R2 is haloalkyl;
- wherein R3 is selected from hydrido, and alkyl;
- and
- wherein R4 is selected from aryl, cycloalkyl, and cycloalkenyl;
- wherein R4 is optionally substituted at a substituable position with one or more radicals selected from halo, alkylthio, alkylsulfinyl, alkyl, alkylsulfonyl, cyano, carboxyl, alkoxycarbonyl, amido, N-monoalkylamido, N-monoarylamido, N,N-dialkylamido, N- alkyl-N-arylamido, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, haloalkoxy, sulfamyl, N- alkylsulfamyl, amino, N-alkylamino, N,N-dialkylamino, heterocyclic, nitro and acylamino;
- or a pharmaceutically-acceptable salt thereof;
- or (b) a compound of the formula
- 7
- wherein R1 is selected from alkyl, carboxyalkyl, alkoxycarbonyl, aminocarbonyl, aminocarbonylalkyl, alkoxycarbonylalkyl, carboxyl, alkoxy, haloalkoxy, aralkoxy, cycloalkylalkoxy, alkylthio, aralkylthio, cycloalkylalkylthio, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, aralkylthioalkyl, alkylaminoalkyl, aryloxyalkyl, arylthioalkyl, hydroxyl, amino, hydroxyalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aralkyl, halo, alkylamino, aralkylamino, N-alkyl-N-aralkylamino, N-alkyl-N-cycloalkylalkylamino, arylcarbonyloxyalkyl, arylcarbonylthio, alkoxycarbonyloxyalkyl, alkylaminocarbonyloxyalkyl, alkoxycarbonylthioalkyl, and alkylaminocarbonylthioalkyl;
- wherein R3 is selected from cycloalkyl, cycloalkenyl, and aryl;
- wherein R3 is optionally substituted at a substitutable position with one or more radicals independently selected from alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, hydroxyalkyl, haloalkoxy, amino, alkylamino, arylamino, aminoalkyl, nitro, alkoxyalkyl, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, halo, alkoxy and alkylthio;
- and
- wherein R4 is selected from lower alkyl, hydroxyl, and amino;
- or a pharmaceutically-acceptable salt thereof;
- and a pharmaceutically acceptable carrier.
14 more elements
A method of treating migraine in a mammal, comprising administering to said mammal a 5HT1 receptor agonist or a pharmaceutically acceptable salt thereof, and caffeine, with (a) a compound of the formula
- 8
- wherein R1 is sulfamyl;
- wherein R2 is haloalkyl;
- wherein R3 is selected from hydrido, and alkyl;
- and
- wherein R4 is selected from aryl, cycloalkyl, and cycloalkenyl;
- wherein R4 is optionally substituted at a substituable position with one or more radicals selected from halo, alkylthio, alkylsulfinyl, alkyl, alkylsulfonyl, cyano, carboxyl, alkoxycarbonyl, amido, N-monoalkylamido, N-monoarylamido, N,N-dialkylamido, N- alkyl-N-arylamido, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, haloalkoxy, sulfamyl, N- alkylsulfamyl, amino, N-alkylamino, N,N-dialkylamino, heterocyclic, nitro and acylamino;
- or a pharmaceutically-acceptable salt thereof;
- or (b) a compound of the formula
- 9
- wherein R1 is selected from alkyl, carboxyalkyl, alkoxycarbonyl, aminocarbonyl, aminocarbonylalkyl, alkoxycarbonylalkyl, carboxyl, alkoxy, haloalkoxy, aralkoxy, cycloalkylalkoxy, alkylthio, aralkylthio, cycloalkylalkylthio, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, aralkylthioalkyl, alkylaminoalkyl, aryloxyalkyl, arylthioalkyl, hydroxyl, amino, hydroxyalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aralkyl, halo, alkylamino, aralkylamino, N-alkyl-N-aralkylamino, N-alkyl-N-cycloalkylalkylamino, arylcarbonyloxyalkyl, arylcarbonylthio, alkoxycarbonyloxyalkyl, alkylaminocarbonyloxyalkyl, alkoxycarbonylthioalkyl, and alkylaminocarbonylthioalkyl;
- wherein R3 is selected from cycloalkyl, cycloalkenyl, and aryl;
- wherein R3 is optionally substituted at a substitutable position with one or more radicals independently selected from alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, hydroxyalkyl, haloalkoxy, amino, alkylamino, arylamino, aminoalkyl, nitro, alkoxyalkyl, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, halo, alkoxy and alkylthio;
- and
- wherein R4 is selected from lower alkyl, hydroxyl, and amino;
- or a pharmaceutically-acceptable salt thereof;
- in amounts that render the combination of such three active agents effective in the treatment of migraine.
14 more elements
Dependencies are inferred from the claim text.