Methods of treating depression using orexin-2 receptor antagonists
The present disclosure is directed to, inter alia, methods of treating a subject suffering from or diagnosed with depression, comprising administering to a subject in need of such treatment an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 1 to R 4 are described herein and wherein the compound is administered prior to sleep.
1. A method of treating depression associated with bipolar disorder in a subject, comprising administering to the subject in need of such treatment an effective amount of a compound of formula (I):
wherein:
R 1 is C 1-4 alkyl;
R 2 is C 1-4 alkyl;
R 3 is H or halogen; and
R 4 is H or C 1-4 alkoxy:
or a pharmaceutically acceptable salt or hydrate thereof.
2. The method of claim 1 , wherein the subject is not suffering from or diagnosed with an insomnia disorder.
3. The method of claim 1 , wherein R 3 is halogen.
4. The method of claim 1 , wherein R 4 is H.
5. The method of claim 1 , wherein the compound is [5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the compound is [5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone.
7. The method of claim 1 , wherein the compound is [5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone hydrochloride.
8. The method of claim 1 , wherein the compound is (5-(4,6-dimethylpyrimidin-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(4-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone or a pharmaceutically acceptable salt thereof.
9. The method of claim 1 , wherein the compound is (5-(4,6-dimethylpyrimidin-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(4-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone.
10. The method of claim 5 , wherein the effective amount of the compound is about 10 to about 40 mg.
11. The method of claim 10 , wherein the compound is administered once daily.
12. The method of claim 11 , wherein the compound is administered at night.
13. The method of claim 11 , wherein the compound is administered prior to sleep.
14. The method of claim 12 , wherein the compound is administered prior to sleep.
15. The method of claim 5 , wherein the effective amount of the compound is about 20 mg.
16. The method of claim 15 , wherein the compound is administered once daily.
17. The method of claim 16 , wherein the compound is administered at night.
18. The method of claim 16 , wherein the compound is administered prior to sleep.
19. The method of claim 17 , wherein the compound is administered prior to sleep.
20. The method of claim 5 , wherein the compound is administered as an adjunctive treatment.
21. The method of claim 20 , wherein the effective amount of the compound is about 10 to about 40 mg.
22. The method of claim 21 , wherein the compound is administered once daily.
23. The method of claim 22 , wherein the compound is administered at night.
24. The method of claim 22 , wherein the compound is administered prior to sleep.
25. The method of claim 23 , wherein the compound is administered prior to sleep.
26. The method of claim 20 , wherein the effective amount of the compound is about 20 mg.
27. The method of claim 26 , wherein the compound is administered once daily.
28. The method of claim 27 , wherein the compound is administered at night.
29. The method of claim 27 , wherein the compound is administered prior to sleep.
30. The method of claim 28 , wherein the compound is administered prior to sleep.