Piperidin-2,6-dione bisulphate salts and their use for the treatment of stress related affective disorders
View Patent ↗Novel bisulphate salts of certain 3-phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-diones and pharmacologically acceptable solvates thereof are devoid of the weight loss and hepatocyte changes in the rat which limited to marginally effective levels the permitted clinical doses of the corresponding hydrochlorides in the treatment or prophylaxis of stress-related affective disorders such as anxiety, depression, migraine and sleep apnea. The preferred bisulphate salts are 3(3,5-dimethoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate and, especially, 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.
1. A bisulphate salt of a 3-phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-dione of Formula I:
wherein:
R 1 represents methoxy, ethoxy or hydroxy;
R 2 represents methoxy, ethoxy, hydroxy or hydrogen; and
n represents 2 or 3, or a pharmacologically acceptable hydrate thereof.
2. A bisulphate salt as claimed in claim 1 , wherein R 1 represents methoxy and R 2 represents methoxy or hydrogen.
3. A bisulphate salt as claimed in claim 2 , wherein the bisulphate salt is 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.
4. A bisulphate salt as claimed in claim 2 , wherein the bisulphate salt is 3(3,5-dimethoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.
5. A bisulphate salt as claimed in claim 1 , wherein the bisulphate salt is in the form of its (−) isomer.
6. A bisulphate salt as claimed in claim 1 , wherein the bisulphate salt is anhydrous.
7. A bisulphate salt as claimed in claim 1 , wherein the bisulphate salt in the form of the sesquihydrate.
8. A pharmaceutical composition comprising a bisulphate salt of a 3-phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-dione of Formula I:
wherein:
R 1 represents methoxy, ethoxy or hydroxy;
R 2 represents methoxy, ethoxy, hydroxy or hydrogen; and
n represents 2 or 3, or a pharmacologically acceptable hydrate thereof and a pharmacologically acceptable diluent or carrier.
9. A pharmaceutical composition as claimed in claim 8 for the treatment or prophylaxis of a stress-related affective disorder.
10. A pharmaceutical composition as claimed in claim 8 , wherein R 1 represents methoxy and R 2 represents methoxy or hydrogen.
11. A pharmaceutical composition as claimed in claim 10 , wherein the bisulphate salt is 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.
12. A pharmaceutical composition as claimed in claim 10 , wherein the bisulphate salt is 3(3,5-dimethoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.
13. A method for the treatment of depression in a human or animal patient in need of such treatment, which comprises administering to the human or animal patient a therapeutically effective amount of a compound of claim 1 .
14. A method for the treatment of anxiety in a human or animal patient in need of such treatment, which comprises administering to the human or animal patient a therapeutically effective amount of a compound of claim 1 .
15. A method for the treatment of sleep apnea in a human or animal patient in need of such treatment, which comprises administering to the human or animal patient a therapeutically effective amount of a compound of claim 1 .
16. A method as claimed in claim 13 , wherein the bisuphate salt is 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.
17. A method as claimed in claim 14 , wherein the bisuphate salt is 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.
18. A method as claimed in claim 15 , wherein the bisuphate salt is 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.
19. A method as claimed in claim 13 , wherein the bisulphate salt is 3(3,5-dimethoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.
20. A method as claimed in claim 14 , wherein the bisulphate salt is 3(3,5-dimethoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.
21. A method as claimed in claim 15 , wherein the bisulphate salt is 3(3,5-dimethoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.