Emesis treatment

Abstract

A method of treating or preventing emesis through the administration of an effective dosage of a 2-(amino) tetralin compound in which one of the S or R enantiomers of the 2-(amino) tetralin compound is present in the composition in excess of the other enantiomer, and compositions comprising such a 2-(amino) tetralin compound in which the ratio of the S and R enantiomers is at least 2:1.

1 . A method for the treatment of emesis in a mammal, comprising the step of administering to the mammal a composition comprising S(−)-8-hydroxy-2-(dipropylamino)tetralin and R(+)-8-hydroxy-2-(dipropylamino)tetralin, wherein one of the S(−)-8-hydroxy-2-(dipropylamino)tetralin enantiomer or the R(+)-8-hydroxy-2-(dipropylamino)tetralin enantiomer is present in the composition in a greater amount than the other enantiomer. 
     
     
         2 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         3 . The method of  claim 1 , wherein the emesis is delayed emesis. 
     
     
         4 . The method of  claim 1 , wherein the emesis is anticipatory emesis. 
     
     
         5 . The method of  claim 1 , wherein the emesis is associated with an event selected from the group consisting of pregnancy, migraine headache, motion, exposure to chemical agents, exposure to radiation, viral infection, bacterial infection. 
     
     
         6 . The method of  claim 1 , wherein the amount of S(−)-8-hydroxy-2-(dipropylamino)tetralin in the composition is greater than the amount of R(+)-8-hydroxy-2-(dipropylamino)tetralin in the composition. 
     
     
         7 . The method of  claim 6 , wherein the ratio of S(−)-8-Hydroxy-2-(dipropylamino)tetralin to R(+)-8-Hydroxy-2-(dipropylamino)tetralin present in the composition is at least 2:1. 
     
     
         8 . The method of  claim 7 , wherein the ratio of S(−)-8-Hydroxy-2-(dipropylamino)tetralin to R(+)-8-Hydroxy-2-(dipropylamino)tetralin present in the composition is at least 8:1. 
     
     
         9 . The method of  claim 1 , wherein the amount of S(−)-8-Hydroxy-2-(dipropylamino)tetralin administered is at least 0.08 mg/kg. 
     
     
         10 . The method of  claim 1 , wherein the amount of S(−)-8-Hydroxy-2-(dipropylamino)tetralin administered is between 0.08 mg/kg and 0.16 mg/kg. 
     
     
         11 . The method of  claim 1 , wherein the amount of R(+)-8-Hydroxy-2-(dipropylamino)tetralin administered is less than 0.04 mg/kg. 
     
     
         12 . A method for the treatment of emesis in a mammal comprising administering to the mammal a composition comprising a mixture of S and R enantiomers of a 2-aminotetralin 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are each, independently, selected from the group consisting of hydrogen, C 1 -C 8  alkyl, and C 1 -C 8  alkenyl, or alternately, R 1  and R 2  can be taken together with the nitrogen to which they are attached to form a 5- to 8-membered nitrocyclic ring, wherein the alkyl, alkenyl, and nitrocyclic groups are unsubstituted, or can be substituted with one or more halide atoms. 
 R 3  is selected from the group consisting of OH, F, NH 2 , CH 3 , and SH; 
 R 4  and R 5  are each, independently, selected from the group consisting of hydrogen, halide, OH, CF 3 , C 1 -C 8  alkyl, and C 1 -C 8  alkenyl, COR 6 , and OR 6 , wherein the alkyl and alkenyl groups are unsubstituted, or can be substituted with one or more halide atoms, and wherein R 4  and R 4  are each, independently substituted at the 1-, 3-, 4-, 5-, 6-, and 7-ring positions of the tetralin ring structure; 
 R 6  is selected from the group consisting of hydrogen, C 1 -C 5  alkyl, C 1 -C 5  alkenyl, and aminoalkyl, and 
 wherein the composition comprises an excess amount of one of the S or R enantiomers of the compound of formula I. 
 
     
     
         13 . The method of  claim 12 , wherein, in the compound of formula I:
 R 1  and R 2  are each independently C 1 -C 8  alkyl;   R 3  is OH; and   R 4  and R 5  are each independently hydrogen, and   wherein the composition comprises an excess amount of the S enantiomer of the compound of formula I.   
     
     
         14 . The method of  claim 12 , wherein R 1  and R 2  are each independently n-propyl. 
     
     
         15 . The method of  claim 12 , wherein the mammal is a human. 
     
     
         16 . A method for the treatment of emesis in a mammal comprising administering to the mammal a composition comprising a mixture of an S enantiomers of a 2-aminotetralin compound and an R enantiomer of a 2-aminotetralin compound, wherein
 the composition comprises an excess amount of at least one of the S enantiomer of the 2-aminotetralin compound or the R enantiomer of the 2-(amino) tetralin compound; and   at least one of the S enantiomer of the 2-aminotetralin compound or the R enantiomer of the 2-(amino) tetralin compound has activity as a 5-HT 1A  agonist.   
     
     
         17 . The method of  claim 16 , wherein the 2-aminotetralin compound is (+)-8-hydroxy-2-(dipropylamino)tetralin. 
     
     
         18 . The method of  claim 17 , wherein the S enantiomer of the 8-hydroxy-2-(dipropylamino)tetralin is present in the composition in an amount greater than the R enantiomer of the 8-hydroxy-2-(dipropylamino)tetralin. 
     
     
         19 . A composition comprising 8-hydroxy-2-(dipropylamino)tetralin wherein the ratio of the S enantiomer of the 8-hydroxy-2-(dipropylamino)tetralin to the R enantiomer of the 8-hydroxy-2-(dipropylamino)tetralin is between 2:1 and 10:1. 
     
     
         20 . The composition of  claim 19 , wherein the ratio of the S enantiomer of the 8-hydroxy-2-(dipropylamino)tetralin to the R enantiomer of the 8-hydroxy-2-(dipropylamino)tetralin is at least 8:1. 
     
     
         21 . The composition of  claim 19 , wherein the ratio of the S enantiomer of the 8-hydroxy-2-(dipropylamino)tetralin to the R enantiomer of the 8-hydroxy-2-(dipropylamino)tetralin is between 4:1 and 8:1. 
     
     
         22 . The composition of  claim 19 , wherein the ratio of the S enantiomer of the 8-hydroxy-2-(dipropylamino)tetralin to the R enantiomer of the 8-hydroxy-2-(dipropylamino)tetralin is 8:1.