Morphinan compounds
This disclosure relates to novel morphinan compounds and their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a σ 1 receptor agonist that also has NMDA antagonist activity.
1. A compound having the formula:
or a pharmaceutically acceptable salt thereof.
2. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.
3. The compound or pharmaceutically acceptable salt thereof of claim 2 , wherein the pharmaceutically acceptable salt is the HBr salt.
4. A pyrogen-free composition comprising the compound or pharmaceutically acceptable salt thereof of claim 2 formulated for pharmaceutical administration and a pharmaceutically acceptable carrier.
5. The composition of claim 4 , further comprising a second therapeutic agent useful in the treatment of a disease or condition selected from pseudobulbar affect and neuropathic pain.
6. The composition of claim 5 , wherein the second therapeutic agent is selected from quinidine or a salt thereof, oxycodone, and gabapentin.
7. The composition of claim 6 , wherein the second therapeutic agent is quinidine or a salt thereof.
8. The composition of claim 7 , wherein the second therapeutic agent is quinidine sulfate.
9. The composition of claim 4 or 5 , wherein the pharmaceutically acceptable salt is the HBr salt.
10. A method of treating a subject suffering from or susceptible to a disease or condition selected from pseudobulbar affect and neuropathic pain, comprising administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound having the formula:
or a pharmaceutically acceptable salt thereof;
and a pharmaceutically acceptable carrier.
11. The method of claim 10 , wherein any atom not designated as deuterium in the compound is present at its natural isotopic abundance.
12. The method of claim 11 , comprising administering to the subject in need thereof a second therapeutic agent selected from quinidine or a salt thereof, oxycodone, and gabapentin.
13. The method of claim 11 , wherein the second therapeutic agent is quinidine or a salt thereof.
14. The method of claim 13 , wherein the subject is suffering from or susceptible to pseudobulbar affect and the second therapeutic agent is quinidine sulfate.
15. The method of claim 11 or 12 , wherein the pharmaceutically acceptable salt is the HBr salt.
16. A composition according to claim 7 , wherein the amount of compound is 10-60 mg and the amount of quinidine is 2.5-30 mg.
17. A composition comprising a compound having the formula:
or a pharmaceutically acceptable salt thereof, wherein the composition is formulated for pharmaceutical administration and wherein the carrier is a pharmaceutically acceptable carrier.
18. The composition of claim 17 , wherein any atom not designated as deuterium in the compound is present at its natural isotopic abundance.
19. The composition of claim 18 , further comprising a second therapeutic agent useful in the treatment of a disease or condition selected from pseudobulbar affect and neuropathic pain .
20. The composition of claim 19 , wherein the second therapeutic agent is selected from quinidine or a salt thereof, oxycodone, and gabapentin.
21. The composition of claim 20 , wherein the second therapeutic agent is quinidine or a salt thereof.
22. The composition of claim 21 , wherein the second therapeutic agent is quinidine sulfate.
23. The composition of claim 18 or 19 , wherein the pharmaceutically acceptable salt is the HBr salt.
24. A method of treating a subject suffering from or susceptible to a disease or condition selected from pseudobulbar affect and neuropathic pain, comprising administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound having the formula:
or a pharmaceutically acceptable salt thereof;
and a pharmaceutically acceptable carrier.
25. The method of claim 24 , wherein any atom not designated as deuterium in the compound is present at its natural isotopic abundance.
26. The method of claim 25 , further comprising administering to the subject in need thereof a second therapeutic agent selected from quinidine or a salt thereof, oxycodone, and gabapentin.
27. The method of claim 26 , wherein the second therapeutic agent is quinidine or a salt thereof
28. The method of claim 27 , wherein the subject is suffering from or susceptible to pseudobulbar affect and the second therapeutic agent is quinidine sulfate.
29. The method of claim 25 or 26 , wherein the pharmaceutically acceptable salt is the HBr salt.
30. A composition according to claim 21 , comprising 10-60 mg of the compound and 2.5-30 mg of quinidine.