Method of treating lower urinary tract disorders
The invention relates to a method of treating at least one symptom of a lower urinary tract disorder in a subject in need of treatment wherein the symptom is selected from the group consisting of urinary frequency, urinary urgency, urinary urge incontinence, nocturia and enuresis. The method comprises administering to a subject in need of treatment a therapeutically effective amount of a compound that has 5-HT 3 receptor antagonist activity and NorAdrenaline Reuptake Inhibitor (NARI) activity. The invention further relates to a method of treating at least one symptom of a lower urinary tract disorder in a subject in need of treatment wherein the symptom is selected from the group consisting of urinary frequency, urinary urgency, urinary urge incontinence, nocturia and enuresis, comprising coadministering to said subject a first amount of a 5-HT 3 antagonist and a second amount of a NARI, wherein the first and second amounts together comprise a therapeutically effective amount or are each present in a therapeutically effective amount.
1 - 70 . (canceled)
71 . A method of treating overactive bladder comprising administering a compound of formula I:
or a pharmaceutically acceptable salt thereof to a human subject in need thereof on an as-needed basis,
wherein R 1 and R 2 independently represent hydrogen, halogen or a C 1 -C 6 alkyl group; or R 1 and R 2 together with the carbon atom to which they are attached form a cycloalkylene group having 5 to 6 carbon atoms;
R 3 and R 4 independently represent hydrogen or a C 1 -C 6 alkyl group;
R 5 is hydrogen, C 1 -C 6 alkyl,
or —C(O)—NH—R 6
wherein m is an integer from about 1 to about 3, X is halogen and R 6 is a C 1 -C 6 alkyl group; and
Ar is a substituted or unsubstituted phenyl, 2-thienyl or 3-thienyl group; and n is 2 or 3.
72 . The method of claim 71 , wherein said as-needed basis is from about 0 minutes to about 10 hours prior to commencement of an activity wherein suppression of overactive bladder is desired.
73 . The method of claim 71 , wherein said as-needed basis is from about 0 minutes to about 5 hours prior to commencement of an activity wherein suppression of overactive bladder is desired.
74 . The method of claim 71 , wherein said as-needed basis is from about 0 minutes to about 3 hours prior to commencement of an activity wherein suppression of overactive bladder is desired.
75 . The method of claim 71 , wherein said as-needed basis is about 10 minutes, about 20 minutes, about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, or about 10 hours prior to commencement of an activity wherein suppression of overactive bladder is desired.
76 . A method of treating overactive bladder comprising administering a compound of formula II:
or a pharmaceutically acceptable salt thereof to a human subject in need thereof on an as-needed basis.
77 . The method of claim 76 , wherein said as-needed basis is from about 0 minutes to about 10 hours prior to commencement of an activity wherein suppression of overactive bladder is desired.
78 . The method of claim 76 , wherein said as-needed basis is from about 0 minutes to about 5 hours prior to commencement of an activity wherein suppression of overactive bladder is desired.
79 . The method of claim 76 , wherein said as-needed basis is from about 0 minutes to about 3 hours prior to commencement of an activity wherein suppression of overactive bladder is desired.
80 . The method of claim 76 , wherein said as-needed basis is about 10 minutes, about 20 minutes, about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, or about 10 hours prior to commencement of an activity wherein suppression of overactive bladder is desired.
81 . A method of treating a lower urinary tract disorder comprising administering a compound of formula I:
or a pharmaceutically acceptable salt thereof to a human subject in need thereof on an as-needed basis,
wherein R 1 and R 2 independently represent hydrogen, halogen or a C 1 -C 6 alkyl group; or R 1 and R 2 together with the carbon atom to which they are attached form a cycloalkylene group having 5 to 6 carbon atoms;
R 3 and R 4 independently represent hydrogen or a C 1 -C 6 alkyl group;
R 5 is hydrogen, C 1 -C 6 alkyl,
or —C(O)—NH—R 6
wherein m is an integer from about 1 to about 3, X is halogen and R 6 is a C 1 -C 6 alkyl group; and
Ar is a substituted or unsubstituted phenyl, 2-thienyl or 3-thienyl group; and n is 2 or 3.
82 . The method of claim 81 , wherein said as-needed basis is from about 0 minutes to about 10 hours prior to commencement of an activity wherein treatment of a lower urinary tract disorder is desired.
83 . The method of claim 81 , wherein said as-needed basis is from about 0 minutes to about 5 hours prior to commencement of an activity wherein treatment of a lower urinary tract disorder is desired.
84 . The method of claim 81 , wherein said as-needed basis is from about 0 minutes to about 3 hours prior to commencement of an activity wherein treatment of a lower urinary tract disorder is desired.
85 . The method of claim 81 , wherein said as-needed basis is about 10 minutes, about 20 minutes, about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, or about 10 hours prior to commencement of an activity wherein treatment of a lower urinary tract disorder is desired.
86 . A method of treating a lower urinary tract disorder comprising administering a compound of formula II:
or a pharmaceutically acceptable salt thereof to a human subject in need thereof on an as-needed basis.
87 . The method of claim 86 , wherein said as-needed basis is from about 0 minutes to about 10 hours prior to commencement of an activity wherein treatment of a lower urinary tract disorder is desired.
88 . The method of claim 86 , wherein said as-needed basis is from about 0 minutes to about 5 hours prior to commencement of an activity wherein treatment of a lower urinary tract disorder is desired.
89 . The method of claim 86 , wherein said as-needed basis is from about 0 minutes to about 3 hours prior to commencement of an activity wherein treatment of a lower urinary tract disorder is desired.
90 . The method of claim 86 , wherein said as-needed basis is about 10 minutes, about 20 minutes, about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, or about 10 hours prior to commencement of an activity wherein treatment of a lower urinary tract disorder is desired.
91 . Use of 4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-D]pyrimidine or a salt thereof for the manufacture of a medicament for the treatment of urinary incontinence.
92 . Use according to claim 91 , wherein the salt is the monohydrate hydrochloride.
93 . Use according to claim 91 or claim 92 , wherein the urinary incontinence is stress urinary incontinence.
94 . A method for the treatment of urinary incontinence in a patient suffering therefrom, comprising administering to the patient an effective amount of 4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-D]pyrimidine or a salt thereof.
95 . The method according to claim 94 , wherein the salt is the monohydrate hydrochloride.
96 . The method according to claim 94 or claim 95 , wherein the urinary incontinence is stress urinary incontinence.