US2003032580A1PendingUtilityA1
Use of agonists or antagonists of the 5-HT7 receptor to treat disorders of the bladder
Est. expiryMay 18, 2019(expired)· nominal 20-yr term from priority
Inventors:Douglas A. Craig
A61K 31/439A61K 31/4045A61K 31/495A61K 31/48A61K 31/404A61K 31/475A61K 31/517A61K 31/496A61K 31/00A61K 31/438
53
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Claims
Abstract
The present invention provides a method of treating urinary incontinence in a subject which comprises administering to the subject a therapeutically effective amount of a 5-HT 7 receptor antagonist or an antagonist that binds to both 5-HT 7 and 5-HT 2B receptors. The invention also provides a method of treating urinary retention in a subject which comprises administering to the subject a therapeutically effective amount of a 5-HT 7 receptor agonist or an agonist that activates both 5-HT 7 and 5-HT 2B receptors.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of treating urinary incontinence in a subject which comprises administering to the subject a therapeutically effective amount of a 5-HT 7 antagonist which binds to the human 5-HT 7 receptor with an affinity at least ten-fold higher than the affinity with which it binds to each of the human 5 -HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
2 . The method of claim 1 , wherein the 5-HT 7 antagonist additionally binds to the human 5-HT 7 receptor with an affinity at least ten-fold higher than the affinity with which it binds to each of the human 5-HT 1B , 5-HT 1D , 5-HT 1E , 5-HT 1F , 5-HT 5A , and 5-HT 5B receptors.
3 . The method of claim 1 , wherein the 5-HT 7 antagonist also binds to the human 5-HT 7 receptor with an affinity at least ten-fold higher than the affinity with which it binds to any human α 2 adrenoceptor or any human β adrenoceptor.
4 . The method of claim 1 , wherein the 5-HT 7 antagonist also binds to the human 5-HT 7 receptor with an affinity at least ten-fold higher than the affinity with which it binds to the human histamine H 1 and H 2 receptors.
5 . The method of claim 1 , wherein the 5-HT 7 antagonist also binds to the human 5-HT 7 receptor with an affinity at least ten-fold higher than the affinity with which it binds to the human dopamine D 1 , D 2 , D 3 , and D 5 receptors.
6 . The method of claim 1 , wherein the 5-HT 7 antagonist also binds to the human 5-HT 7 receptor with an affinity at least ten-fold higher than the affinity with which it binds to the human α 1A adrenoceptor and the human α 1B adrenoceptor.
7 . The method of claim 1 , wherein the 5-HT 7 antagonist binds to the human 5-HT 7 receptor with an affinity at least 50-fold higher than the affinity with which it binds to each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
8 . The method of claim 7 , wherein the 5-HT 7 antagonist binds to the human 5-HT 7 receptor with an affinity at least 100-fold higher than the affinity with which it binds to each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
9 . The method of claim 8 , wherein the 5-HT 7 antagonist binds to the human 5-HT 7 receptor with an affinity at least 200-fold higher than the affinity with which it binds to each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
10 . The method of claim 1 , wherein the 5-HT 7 antagonist is also a 5-HT 2B antagonist which binds to the human 5-HT 2B receptor with an affinity at least 10-fold higher than the affinity with which it binds to each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
11 . The method of claim 10 , wherein the 5-HT 7 antagonist additionally binds to the human 5-HT 2B receptor with an affinity at least ten-fold higher than the affinity with which it binds to each of the human 5-HT 1B , 5-HT 1D , 5-HT 1E , 5-HT 1F , 5-HT 5A , and 5-HT 5B receptors.
12 . The method of claim 10 , wherein the 5-HT 7 antagonist binds to the human 5-HT 2B receptor with an affinity at least 50-fold higher than the affinity with which it binds to each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
13 . The method of claim 12 , wherein the 5-HT 7 antagonist binds to the human 5-HT 2B receptor with an affinity at least 100-fold higher than the affinity with which it binds to each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
14 . The method of claim 13 , wherein the 5-HT 7 antagonist binds to the human 5-HT 2B receptor with an affinity at least 200-fold higher than the affinity with which it binds to each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
15 . The method of claim 10 , wherein the 5-HT 7 antagonist is a 5-HT 2B antagonist which binds to the human 5-HT 2B receptor with an affinity at least ten-fold higher than the affinity with which it binds to any human α 2 adrenoceptor or any human β adrenoceptor.
16 . The method of claim 10 , wherein the 5-HT 7 antagonist is a 5-HT 2B antagonist which binds to the human 5-HT 2B receptor with an affinity at least ten-fold higher than the affinity with which it binds to the human histamine H 1 and H 2 receptors.
17 . The method of claim 10 , wherein the 5-HT 7 antagonist is a 5-HT 2B antagonist which binds to the human 5-HT 2B receptor with an affinity at least ten-fold higher than the affinity with which it binds to the human dopamine D 1 , D 2 , D 3 , and D 5 receptors.
18 . The method of claim 10 , wherein the 5-HT 7 antagonist is a 5-HT 2B antagonist which binds to the human 5-HT 2B receptor with an affinity at least ten-fold higher than the affinity with which it binds to the human α 1A adrenoceptor and the human α 1B adrenoceptor.
19 . A method of treating urinary retention in a subject which comprises administering to the subject a therapeutically effective amount of a 5-HT 7 agonist which activates the human 5-HT 7 receptor at least ten-fold more than it activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
20 . The method of claim 19 , wherein the 5-HT 7 agonist additionally activates the human 5-HT 7 receptor at least ten-fold more than it activates each of the human 5-HT 1B , 5-HT 1D , 5-HT 1E , 5-HT 1F , 5-HT 5A , and 5-HT 5B receptors.
21 . The method of claim 19 , wherein the 5-HT 7 agonist also activates the human 5-HT 7 receptor at least ten-fold more than it activates any human α 2 adrenoceptor or any human β adrenoceptor.
22 . The method of claim 19 , wherein the 5-HT 7 agonist also activates the human 5-HT 7 receptor at least ten-fold more than it activates the human histamine H 1 and H 2 receptors.
23 . The method of claim 19 , wherein the 5-HT 7 agonist also activates the human 5-HT 7 receptor at least ten-fold more than it activates the human dopamine D 1 , D 2 , D 3 , and D 5 receptors.
24 . The method of claim 19 , wherein the 5-HT 7 agonist also activates the human 5-HT 7 receptor at least ten-fold more than it activates the human α 1A adrenoceptor and the human α 1B adrenoceptor.
25 . The method of claim 19 , wherein the 5-HT 7 agonist activates the human 5-HT 7 receptor at least 50-fold more than it activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
26 . The method of claim 25 , wherein the 5-HT 7 agonist activates the human 5-HT 7 receptor at least 100-fold more than it activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
27 . The method of claim 26 , wherein the 5-HT 7 agonist activates the human 5-HT 7 receptor at least 200-fold more than it activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
28 . The method of claim 19 , wherein the 5-HT 7 agonist is also a 5-HT 2B agonist which activates the human 5-HT 2B receptor at least ten-fold more than it activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
29 . The method of claim 28 , wherein the 5-HT 7 agonist additionally activates the human 5-HT 2B receptor at least ten-fold more than it activates each of the human 5-HT 1B , 5-HT 1D , 5-HT 1E , 5-HT 1F , 5-HT 5A , and 5-HT 5B receptors.
30 . The method of claim 28 , wherein the 5-HT 7 agonist activates the human 5-HT 2B receptor at least 50-fold more than it activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
31 . The method of claim 30 wherein the 5-HT 7 agonist activates the human 5-HT 2B receptor at least 100-fold more than it activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
32 . The method of claim 31 , wherein the 5-HT 7 agonist activates the human 5-HT 2B receptor at least 200-fold more than it activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
33 . The method of claim 28 , wherein the 5-HT 7 agonist is a 5-HT 2B agonist which activates the human 5-HT 2B receptor at least ten-fold more than it activates any human α 2 adrenoceptor or any human β adrenoceptor.
34 . The method of claim 28 , wherein the 5-HT 7 agonist is a 5-HT 2B agonist which activates the human 5-HT 2B receptor at least ten-fold more than it activates the human histamine H 1 and H 2 receptors.
35 . The method of claim 28 , wherein the 5-HT 7 agonist is a 5-HT 2B agonist which activates the human 5-HT 2B receptor at least ten-fold more than it activates the human dopamine D 1 , D 2 , D 3 , and D 5 receptors.
36 . The method of claim 28 , wherein the 5-HT 7 agonist is a 5-HT 2B agonist which activates the human 5-HT 2B receptor at least ten-fold more than it activates the human α 1A adrenoceptor and the human α 1B adrenoceptor.
37 . A method of treating urinary incontinence in a subject which comprises administering to the subject a therapeutically effective amount of an admixture of a 5-HT 7 antagonist and a 5-HT 2B antagonist, wherein both the affinity with which the 5-HT 7 antagonist binds to the human 5-HT 7 receptor and the affinity with which the 5-HT 2B antagonist binds to the human 5-HT 2B receptor are at least ten-fold higher than the affinity with which each antagonist binds to each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
38 . The method of claim 37 , wherein the 5-HT 7 antagonist additionally binds to the human 5-HT 7 receptor and the 5-HT 2B antagonist additionally binds to the human 5-HT 2B receptor with an affinity at least ten-fold higher than the affinity with which each antagonist binds to each of the human 5-HT 1B , 5-HT 1D , 5-HT 1E , 5-HT 1F , 5-HT 5A , and 5-HT 5B receptors.
39 . The method of claim 37 , wherein at least one of the affinity with which the 5-HT 7 antagonist binds to the human 5-HT 7 receptor or the affinity with which the 5-HT 2B antagonist binds to the human 5-HT 2B receptor is at least ten-fold higher than the affinity with which said antagonist binds to any human α 2 adrenoceptor or any human β adrenoceptor.
40 . The method of claim 37 , wherein at least one of the affinity with which the 5-HT 7 antagonist binds to the human 5-HT 7 receptor or the affinity with which the 5-HT 2B antagonist binds to the human 5-HT 2B receptor is at least ten-fold higher than the affinity with which said antagonist binds to the human histamine H 1 and H 2 receptors.
41 . The method of claim 37 , wherein at least one of the affinity with which the 5-HT 7 antagonist binds to the human 5-HT 7 receptor or the affinity with which the 5-HT 2B antagonist binds to the human 5-HT 2B receptor is at least ten-fold higher than the affinity with which said antagonist binds to the human dopamine D 1 , D 2 , D 3 , and D 5 receptors.
42 . The method of claim 37 , wherein at least one of the affinity with which the 5-HT 7 antagonist binds to the human 5-HT 7 receptor or the affinity with which the 5-HT 2B antagonist binds to the human 5-HT 2B receptor is at least ten-fold higher than the affinity with which said antagonist binds to the human α 1A adrenoceptor and the human α 1B adrenoceptor.
43 . The method of claim 37 , wherein at least one of the affinity with which the 5-HT 7 antagonist binds to the human 5-HT 7 receptor or the affinity with which the 5-HT 2B antagonist binds to the human 5-HT 2B receptor is at least 50-fold higher than the affinity with which said antagonist binds to each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
44 . The method of claim 43 , wherein at least one of the affinity with which the 5-HT 7 antagonist binds to the human 5-HT 7 receptor or the affinity with which the 5-HT 2B antagonist binds to the human 5-HT 2B receptor is at least 100-fold higher than the affinity with which said antagonist binds to each of the human 5 -HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
45 . The method of claim 44 , wherein at least one of the affinity with which the 5-HT 7 antagonist binds to the human 5-HT 7 receptor or the affinity with which the 5-HT 2B antagonist binds to the human 5-HT 2B receptor is at least 200-fold higher than the affinity with which said antagonist binds to each of the human 5 -HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
46 . A method of treating urinary retention in a subject which comprises administering to the subject a therapeutically effective amount of an admixture of a 5-HT 7 agonist and a 5-HT 2B , agonist, wherein both the 5-HT 7 agonist activates the human 5-HT 7 receptor and the 5-HT 2B agonist activates the human 5-HT 2B receptor at least ten-fold more than the extent to which each agonist activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
47 . The method of claim 46 , wherein the 5-HT 7 agonist additionally activates the human 5-HT 7 receptor and the 5-HT 2B agonist additionally activates the human 5-HT 2B receptor at least ten-fold more than the extent to which each agonist activates each of the human 5-HT 1B , 5-HT 1D , 5-HT 1E , 5-HT 1F , 5-HT 5A , and 5-HT 5B receptors.
48 . The method of claim 46 , wherein at least one of the extent to which the 5-HT 7 agonist activates the human 5-HT 7 receptor or the extent to which the 5-HT 2B agonist activates the human 5-HT 2B receptor is at least ten-fold more than the extent to which said agonist activates any human α 2 adrenoceptor or any human β adrenoceptor.
49 . The method of claim 46 , wherein at least one of the extent to which the 5-HT 7 agonist activates the human 5-HT 7 receptor or the extent to which the 5-HT 2B agonist activates the human 5-HT 2B receptor is at least ten-fold more than the extent to which said agonist activates the human histamine H 1 and H 2 receptors.
50 . The method of claim 46 , wherein at least one of the extent to which the 5-HT 7 agonist activates the human 5-HT7 receptor or the extent to which the 5-HT 2B agonist activates the human 5-HT 2B receptor is at least ten-fold more than the extent to which said agonist activates the human dopamine D 1 , D 2 , D 3 , and D 5 receptors.
51 . The method of claim 46 , wherein at least one of the extent to which the 5-HT 7 agonist activates the human 5-HT 7 receptor or the extent to which the 5-HT 2B agonist activates the human 5-HT 2B receptor is at least ten-fold more than the extent to which said agonist activates the human α 1A adrenoceptor and the human α 1B adrenoceptor.
52 . The method of claim 46 , wherein at least one of the extent to which the 5-HT 7 agonist activates the human 5-HT 7 receptor or the extent to which the 5-HT 2B agonist activates the human 5-HT 2B receptor is at least 50-fold more than the extent to which said agonist activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
53 . The method of claim 52 , wherein at least one of the extent to which the 5-HT 7 agonist activates the human 5-HT 7 receptor or the extent to which the 5 -HT 2B agonist activates the human 5-HT 2B receptor is at least 100-fold more than the extent to which said agonist activates each of the human 5 -HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.
54 . The method of claim 53 , wherein at least one of the extent to which the 5-HT 7 agonist activates the human 5-HT 7 receptor or the extent to which the 5-HT 2B agonist activates the human 5-HT 2B receptor is at least 200-fold more than the extent to which said agonist activates each of the human 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 , 5-HT 4 , and 5-HT 6 receptors.Join the waitlist — get patent alerts
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