Method for inhibiting detrusor muscle overactivity
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 inhibiting detrusor muscle overactivity comprising administering a compound of formula I:
or a pharmaceutically acceptable salt thereof to a human subject in need thereof, 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 administering is oral.
73 . The method of claim 71 , wherein said administering is on an as-needed basis.
74 . The method of claim 71 , wherein said therapeutically effective amount is from about 0.001 to about 1000 mg per day.
75 . The method of claim 71 , wherein said therapeutically effective amount is from about 0.05 to about 500 mg per day.
76 . The method of claim 71 , wherein said therapeutically effective amount is from about 0.03 to about 300 mg per day.
77 . The method of claim 71 , wherein said therapeutically effective amount is from about 0.02 to about 200 mg per day.
78 . The method of claim 71 , wherein said therapeutically effective amount is from about 0.1 to about 50 mg per day.
79 . The method of claim 71 , wherein said detrusor muscle overactivity is associated with stroke, Parkinson's disease, diabetes, multiple sclerosis, peripheral neuropathy, a spinal cord lesion, bladder stones, muscle disease, an urinary tract infection or a drug side effect.
80 . A method of inhibiting detrusor muscle overactivity comprising administering a compound of formula II:
or a pharmaceutically acceptable salt thereof to a human subject in need thereof.
81 . The method of claim 80 , wherein said administering is oral.
82 . The method of claim 80 , wherein said administering is on an as-needed basis.
83 . The method of claim 80 , wherein said therapeutically effective amount is from about 0.001 to about 1000 mg per day.
84 . The method of claim 80 , wherein said therapeutically effective amount is from about 0.05 to about 500 mg per day.
85 . The method of claim 80 , wherein said therapeutically effective amount is from about 0.03 to about 300 mg per day.
86 . The method of claim 80 , wherein said therapeutically effective amount is from about 0.02 to about 200 mg per day.
87 . The method of claim 80 , wherein said therapeutically effective amount is from about 0.1 to about 50 mg per day.
88 . The method of claim 80 , wherein said detrusor muscle overactivity is associated with stroke, Parkinson's disease, diabetes, multiple sclerosis, peripheral neuropathy, a spinal cord lesion, bladder stones, muscle disease, an urinary tract infection or a drug side effect.
89 . A method of promoting detrusor muscle stability comprising administering a compound of formula I:
or a pharmaceutically acceptable salt thereof to a human subject in need thereof, 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.
90 . The method of claim 89 , wherein said administering is oral.
91 . The method of claim 89 , wherein said administering is on an as-needed basis.
92 . The method of claim 89 , wherein said therapeutically effective amount is from about 0.001 to about 1000 mg per day.
93 . The method of claim 89 , wherein said therapeutically effective amount is from about 0.05 to about 500 mg per day.
94 . The method of claim 89 , wherein said therapeutically effective amount is from about 0.03 to about 300 mg per day.
95 . The method of claim 89 , wherein said therapeutically effective amount is from about 0.02 to about 200 mg per day.
96 . The method of claim 89 , wherein said therapeutically effective amount is from about 0.1 to about 50 mg per day.
97 . The method of claim 89 , wherein said detrusor muscle stability is desired in a subject with bladder stones, muscle disease, an urinary tract infection or a drug side effect.
98 . A method of promoting detrusor muscle stability comprising administering a compound of formula II:
or a pharmaceutically acceptable salt thereof to a human subject in need thereof.
99 . The method of claim 98 , wherein said administering is oral.
100 . The method of claim 98 , wherein said administering is on an as-needed basis.
101 . The method of claim 98 , wherein said therapeutically effective amount is from about 0.001 to about 1000 mg per day.
102 . The method of claim 98 , wherein said therapeutically effective amount is from about 0.05 to about 500 mg per day.
103 . The method of claim 98 , wherein said therapeutically effective amount is from about 0.03 to about 300 mg per day.
104 . The method of claim 98 , wherein said therapeutically effective amount is from about 0.02 to about 200 mg per day.
105 . The method of claim 98 , wherein said therapeutically effective amount is from about 0.1 to about 50 mg per day.
106 . The method of claim 98 , wherein said detrusor muscle stability is desired in a subject with bladder stones, muscle disease, an urinary tract infection or a drug side effect.