Methods and compositions for treating addiction disorders

• US 6,780,871 B2
• Filed: 01/18/2002
• Issued: 08/24/2004
• Est. Priority Date: 01/29/2001
• Status: Active Grant

• Current Assignee: Albany Medical College (Albany Medical Center)
• Original Assignee: Albany Medical College (Albany Medical Center)
• Inventors: Glick, Stanley D., Maisonneuve, Isabelle M.
• Primary Examiner(s): Seidel, Marianne C.
• Assistant Examiner(s): KWON, YONG SOK
• Application Number:
  US10/051,770
• Publication Number:
  US 20020103109A1
• Time in Patent Office: 949 Days
• Field of Search: 514/343, 514/282, 514/214.03, 514/226.2
• US Class Current: 514/282
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

A method for treating an addiction disorder (such as an addiction to or dependency on stimulants, nicotine, morphine, heroin, other opiates, amphetamines, cocaine, and/or alcohol) in a patient is disclosed. The method includes administering to the patient a first α₃β₄ nicotinic receptor antagonist and administering to the patient a second α₃β₄ nicotinic receptor antagonist. The second α₃β₄ nicotinic receptor antagonist is different than the first α₃β₄ nicotinic receptor antagonist, and the first α₃β₄ nicotinic receptor antagonist and the second α₃β₄ nicotinic receptor antagonist are administered simultaneously or non-simultaneously. Compositions which include a first α₃β₄ nicotinic receptor antagonist and a second α₃β₄ nicotinic receptor antagonist are also described. Examples of suitable α₃β₄ nicotinic receptor antagonists for use in the present invention'"'"'s methods and compositions include mecamylamine, 18-methoxycoronaridine, bupropion, dextromethorphan, dextrorphan, and phamaceutically acceptable salts and solvates thereof. A method of evaluating a compound for its effectiveness in treating addiction disorders is also described.

Claims

1. A composition comprising a first α

₃β

₄ nicotinic receptor antagonist and a second α

₃β

₄ nicotinic receptor antagonist, wherein said first α

₃β

₄ nicotinic receptor antagonist is 18-methoxycoronaridine or a pharmaceutically acceptable salt or solvate thereof and said second α

₃β

₄ nicotinic receptor antagonist is mecamylamine or a pharmaceutically acceptable salt or solvate thereof.

2. A composition according to claim 1, wherein said first α

₃β

₄ nicotinic receptor antagonist and said second α

₃β

₄ nicotinic receptor antagonist are present in a weight ratio of from about 10;

1 to about 1;

10.

3. A composition according to claim 1, wherein said first α

₃β

₄ nicotinic receptor antagonist and said second α

₃β

₄ nicotinic receptor antagonist are present in a weight ratio of from about 5;

1 to about 1;

5.

4. A composition according to claim 1, wherein said composition is in the form of a tablet, capsule, granular dispersible powder, suspension, syrup, or elixir.

5. A composition according to claim 1, wherein said composition is in the form of a tablet or capsule and wherein said composition further comprises an inert diluent, a granulating agent, a disintegrating agent, a lubricating agent, or combinations thereof.

6. A method for treating nicotine addiction in a patient, said method comprising:

administering to the patient a composition according to claim 1.

7. A method according to claim 6, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

8. A method according to claim 6, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

9. A method for treating amphetamine addiction in a patient, said method comprising:

administering to the patient a composition according to claim 1.

10. A method according to claim 9, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

11. A method according to claim 9, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

12. A method for treating opioid addiction in a patient, said method comprising:

administering to the patient a composition according to claim 1.

13. A method according to claim 12, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

14. A method according to claim 12, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

15. A composition comprising a first α

₃β

₄ nicotinic receptor antagonist and a second α

₃β

₄ nicotinic receptor antagonist, wherein said first α

₃β

₄ nicotinic receptor antagonist is 18-methoxycoronaridine or a pharmaceutically acceptable salt or solvate thereof and said second α

₃β

₄ nicotinic receptor antagonist is dextromethorphan or a pharmaceutically acceptable salt or solvate thereof.

16. A composition according to claim 15, wherein said first α

₃β

₄ nicotinic receptor antagonist and said second α

₃β

₄ nicotinic receptor antagonist are present in a weight ratio of from about 10;

1 to about 1;

10.

17. A composition according to claim 15, wherein said first α

₃β

₄ nicotinic receptor antagonist and said second α

₃β

₄ nicotinic receptor antagonist are present in a weight ratio of from about 5;

1 to about 1;

5.

18. A composition according to claim 15, wherein said composition is in the form of a tablet, capsule, granular dispersible powder, suspension, syrup, or elixir.

19. A composition according to claim 15, wherein said composition is in the form of a tablet or capsule and wherein said composition further comprises an inert diluent, a granulating agent, a disintegrating agent, a lubricating agent, or combinations thereof.

20. A method for treating nicotine addiction in a patient, said method comprising:

administering to the patient a composition according to claim 15.

21. A method according to claim 20, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

22. A method according to claim 20, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

23. A method for treating amphetamine addiction in a patient, said method comprising:

administering to the patient a composition according to claim 15.

24. A method according to claim 23, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

25. A method according to claim 23, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

26. A method for treating opioid addiction in a patient, said method comprising:

administering to the patient a composition according to claim 15.

27. A method according to claim 25, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

28. A method according to claim 26, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

29. A composition comprising a first α

₃β

₄ nicotinic receptor antagonist and a second α

₃β

₄ nicotinic receptor antagonist, wherein said first α

₃β

₄ nicotinic receptor antagonist is 18-methoxycoronaridine or a pharmaceutically acceptable salt or solvate thereof and said second α

₃β

₄ nicotinic receptor antagonist is bupropion or a pharmaceutically acceptable salt or solvate thereof.

30. A composition according to claim 29, wherein said first α

₃β

₄ nicotinic receptor antagonist and said second α

₃β

₄ nicotinic receptor antagonist are present in a weight ratio of from about 10;

1 to about 1;

10.

31. A composition according to claim 29, wherein said first α

₃β

₄ nicotinic receptor antagonist and said second α

₃β

₄ nicotinic receptor antagonist are present in a weight ratio of from about 5;

1 to about 1;

5.

32. A composition according to claim 29, wherein said composition is in the form of a tablet, capsule, granular dispersible powder, suspension, syrup, or elixir.

33. A composition according to claim 29, wherein said composition is in the form of a tablet or capsule and wherein said composition further comprises an inert diluent, a granulating agent, a disintegrating agent, a lubricating agent, or combinations thereof.

34. A method for treating nicotine addiction in a patient, said method comprising:

administering to the patient a composition according to claim 29.

35. A method according to claim 34, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

36. A method according to claim 34, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

37. A method for treating amphetamine addiction in a patient, said method comprising:

administering to the patient a composition according to claim 29.

38. A method according to claim 37, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

39. A method according to claim 37, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

40. A method for treating opioid addiction in a patient, said method comprising:

administering to the patient a composition according to claim 29.

41. A method according to claim 40, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patients body weight per day.

42. A method according to claim 40, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

43. A composition comprising a first α

₃β

₄ nicotinic receptor antagonist and a second α

₃β

₄ nicotinic receptor antagonist, wherein said first α

₃β

₄ nicotinic receptor antagonist is mecamylamine or a pharmaceutically acceptable salt or solvate thereof and said second α

₃β

₄ nicotinic receptor antagonist is dextromethorphan or a pharmaceutically acceptable salt or solvate thereof.

44. A composition according to claim 43, wherein said first α

₃β

₄ nicotinic receptor antagonist and said second α

₃β

₄ nicotinic receptor antagonist are present in a weight ratio of from about 10;

1 to about 1;

10.

45. A composition according to claim 43, wherein said first α

₃β

₄ nicotinic receptor antagonist and said second α

₃β

₄ nicotinic receptor antagonist are present in a weight ratio of from about 5;

1 to about 1;

5.

46. A composition according to claim 43, wherein said composition is in the form of a tablet, capsule, granular dispersible powder, suspension, syrup, or elixir.

47. A composition according to claim 43, wherein said composition is in the form of a tablet or capsule and wherein said composition further comprises an inert diluent, a granulating agent, a disintegrating agent, a lubricating agent, or combinations thereof.

48. A method for treating nicotine addiction in a patient, said method comprising:

administering to the patient a composition according to claim 43.

49. A method according to claim 48, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

50. A method according to claim 48, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

51. A method for treating amphetamine addiction in a patient, said method comprising:

administering to the patient a composition according to claim 43.

52. A method according to claim 51, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

53. A method according to claim 51, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.

54. A method for treating opioid addiction in a patient, said method comprising:

administering to the patient a composition according to claim 43.

55. A method according to claim 54, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.01 to about 10 mg/kg of the patient'"'"'s body weight per day.

56. A method according to claim 54, wherein the first α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day and wherein the second α

₃β

₄ nicotinic receptor antagonist is administered in an amount of from about 0.1 to about 5 mg/kg of the patient'"'"'s body weight per day.