Methods of inducing bronchodilation

Claim 1

A method for inducing bronchodilation in a mammal which comprises administering: (a) a subthreshold bronchodilating effective amount of forskolin or a forskolin derivative chosen from those having the structural formula I, ##STR16## wherein R 1 and R 2 may be the same or different and are ═O, H, or OR 11 wherein R 11 is H, carboxylic acyl having from 1 to 6 carbon atoms or ##STR17## wherein m is 0, 1, 2 or 3 and Y is hydrogen, halogen, alkyl having from 1 to 6 carbon atoms, alkoxy having from 1 to 6 carbon atoms, alkylthio having from 1 to 6 carbon atoms, OH, CF 3 , NO 2 , CN, phenyl, benzyl, phenoxy or NR a R b wherein R a and R b are the same or different and are H or alkyl having from 1 to 6 carbon atoms; R 1 and R 2 when together may form ##STR18## wherein R 13 and R 14 may be the same or different and are H, alkyl having from 1 to 6 carbon atoms, alkenyl having from 2 to 6 carbon atoms, alkynyl having from 2 to 6 carbon atoms or ##STR19## wherein m and Y are defined above; R 3 is hydrogen; alkyl having from 1 to 10 carbon atoms; CH 2 OH; CHO; CO 2 R 15 wherein R 15 is H or alkyl having from 1 to 6 carbon atoms; --CH═CR 16 R 17 wherein R 16 is H, halogen, alkyl having from 1 to 6 carbon atoms, ##STR20## wherein n is O or 1 and R c is H, alkyl having from 1 to 6 carbon atoms, 1 phenyl or benzyl, CHOHR c or C(OR d ) 2 R c wherein R c is defined above and R d is alkyl having from 1 to 6 carbon atoms, R 17 is H, alkyl having from 1 to 6 carbon atoms, alkoxy having from 1 to 6 carbon atoms, benzyl, phenyl or halogen; --C.tbd.C--R 18 wherein R 18 is H, alkyl having from 1 to 12 carbon atoms, alkoxy having from 1 to 6 carbon atoms or ##STR21## wherein Y is defined above; --CHOH--C.tbd.C--R 19 wherein R 19 is H, alkyl of from 1 to 6 carbon atoms, phenyl or benzyl; --CH═C═CHR 19 wherein R 19 is defined above; --CH═N--OR 19 wherein R 19 is defined above; ##STR22## wherein Z is O or S, and R 16 and R 19 are defined above; --CH(ZR 20 ) 2 wherein Z is defined above and R 20 is alkyl having from 1 to 6 carbon atoms, phenyl, benzyl or the two groups R 20 may together form --(CH 2 )1 p --wherein p is 2 or 3; ##STR23## wherein A and B are H, halogen, alkyl having from 1 to 6 carbon atoms, phenyl, benzyl or ##STR24## wherein n and R c are defined above; --CH═N--NDE wherein D and E are H, alkyl having from 1 to 6 carbon atoms, benzyl, phenyl, CoG, SO 2 G wherein G is alkyl having form 1 to 6 carbon atoms, benzyl or phenyl; R 4 is H or OH; R 5 is OH; or when R 4 and R 5 are taken together they may form ##STR25## wherein Z is defined above; a is an optional bond which may be located in either the 5, 6 or 6, 7 position; and X is O or H/OH; and (b) a subthreshold bronchodilating effective amount of a beta adrenergic agonist chosen from among isoproterenol, terbutaline, metaproterenol and albuterol; to said mammal.

Claim 2

A method for inducing bronchodilation in a mammal which comprises administering: (a) a subthreshold bronchodilating effective amount of forskolin or a forskolin derivative chosen from those having the structural formula I, ##STR16## wherein R 1 and R 2 may be the same or different and are ═O, H, or OR 11 wherein R 11 is H, carboxylic acyl having from 1 to 6 carbon atoms or ##STR17## wherein m is 0, 1, 2 or 3 and Y is hydrogen, halogen, alkyl having from 1 to 6 carbon atoms, alkoxy having from 1 to 6 carbon atoms, alkylthio having from 1 to 6 carbon atoms, OH, CF 3 , NO 2 , CN, phenyl, benzyl, phenoxy or NR a R b wherein R a and R b are the same or different and are H or alkyl having from 1 to 6 carbon atoms; R 1 and R 2 when together may form ##STR18## wherein R 13 and R 14 may be the same or different and are H, alkyl having from 1 to 6 carbon atoms, alkenyl having from 2 to 6 carbon atoms, alkynyl having from 2 to 6 carbon atoms or ##STR19## wherein m and Y are defined above; R 3 is hydrogen; alkyl having from 1 to 10 carbon atoms; CH 2 OH; CHO; CO 2 R 15 wherein R 15 is H or alkyl having from 1 to 6 carbon atoms; --CH═CR 16 R 17 wherein R 16 is H, halogen, alkyl having from 1 to 6 carbon atoms, ##STR20## wherein n is O or 1 and R c is H, alkyl having from 1 to 6 carbon atoms, 1 phenyl or benzyl, CHOHR c or C(OR d ) 2 R c wherein R c is defined above and R d is alkyl having from 1 to 6 carbon atoms, R 17 is H, alkyl having from 1 to 6 carbon atoms, alkoxy having from 1 to 6 carbon atoms, benzyl, phenyl or halogen; --C.tbd.C--R 18 wherein R 18 is H, alkyl having from 1 to 12 carbon atoms, alkoxy having from 1 to 6 carbon atoms or ##STR21## wherein Y is defined above; --CHOH--C.tbd.C--R 19 wherein R 19 is H, alkyl of from 1 to 6 carbon atoms, phenyl or benzyl; --CH═C═CHR 19 wherein R 19 is defined above; --CH═N--OR 19 wherein R 19 is defined above; ##STR22## wherein Z is O or S, and R 16 and R 19 are defined above; --CH(ZR 20 ) 2 wherein Z is defined above and R 20 is alkyl having from 1 to 6 carbon atoms, phenyl, benzyl or the two groups R 20 may together form --(CH 2 )1 p --wherein p is 2 or 3; ##STR23## wherein A and B are H, halogen, alkyl having from 1 to 6 carbon atoms, phenyl, benzyl or ##STR24## wherein n and R c are defined above; --CH═N--NDE wherein D and E are H, alkyl having from 1 to 6 carbon atoms, benzyl, phenyl, CoG, SO 2 G wherein G is alkyl having form 1 to 6 carbon atoms, benzyl or phenyl; R 4 is H or OH; R 5 is OH; or when R 4 and R 5 are taken together they may form ##STR25## wherein Z is defined above; a is an optional bond which may be located in either the 5, 6 or 6, 7 position; and X is O or H/OH; and (b) a subthreshold bronchodilating effective amount of a beta adrenergic agonist chosen from among isoproterenol, terbutaline, metaproterenol and albuterol; to said mammal.