Method for inhibiting detrusor muscle overactivity

• US 20050272719A1
• Filed: 05/04/2005
• Published: 12/08/2005
• Est. Priority Date: 04/04/2003
• Status: Abandoned Application

• Current Assignee: Dynogen Pharmaceuticals, Inc. (Edusa Pharmaceuticals, Inc.)
• Original Assignee: Dynogen Pharmaceuticals, Inc. (Edusa Pharmaceuticals, Inc.)
• Inventors: Landau, Steven B., Fraser, Matthew O., Miller, Cheryl L.
• Application Number:
  US11/122,940
• Publication Number:
  US 20050272719A1
• Time in Patent Office: Days
• US Class Current: 514/218
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

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-HT₃ 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-HT₃ 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.

Claims

1-70. -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 R₁ and R₂ independently represent hydrogen, halogen or a C₁-C₆ alkyl group;

or R₁ and R₂ together with the carbon atom to which they are attached form a cycloalkylene group having 5 to 6 carbon atoms;

R₃ and R₄ independently represent hydrogen or a C₁-C₆ alkyl group;

R₅ is hydrogen, C₁-C₆ alkyl,

or —

C(O)—

NH—

R₆

wherein m is an integer from about 1 to about 3, X is halogen and R₆ is a C₁-C₆ 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 R₁ and R₂ independently represent hydrogen, halogen or a C₁-C₆ alkyl group;

or R₁ and R₂ together with the carbon atom to which they are attached form a cycloalkylene group having 5 to 6 carbon atoms;

R₃ and R₄ independently represent hydrogen or a C₁-C₆ alkyl group;

R₅ is hydrogen, C₁-C₆ alkyl,

or —

C(O)—

NH—

R₆

wherein m is an integer from about 1 to about 3, X is halogen and R₆ is a C₁-C₆ 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.