Therapeutic Combinations

• US 20080085888A1
• Filed: 09/14/2007
• Published: 04/10/2008
• Est. Priority Date: 09/15/2006
• Status: Abandoned Application

• Current Assignee: Astrazeneca AB (Astrazeneca PLC), Targacept, Inc. (Catalyst Biosciences, Inc.)
• Original Assignee: Targacept, Inc. (Catalyst Biosciences, Inc.)
• Inventors: Miller, Craig, Mrzljak, Ladislav, Johnson, Edwin, Evenden, John, Letchworth, Sharon, Jordan, Kristen, Wamsley, James, Widzowski, Dan, Breining, Scott, Xiao, Yun-De
• Application Number:
  US11/855,175
• Publication Number:
  US 20080085888A1
• Time in Patent Office: Days
• US Class Current: 514/211.13
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/451 having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• CPC Class Codes: A61K 31/554 having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Abstract

The present invention provides a combination of (a) an antipsychotic and (b) an alpha4/beta2 (α4β2)-neuronal nicotinic receptor agonist. The invention further relates to pharmaceutical compositions comprising said combination and to the use of the combination in therapy. The invention further relates to a kit comprising the combination and use of said kit in therapy.

Claims

1. A combination comprising:

an antipsychotic agent, or a pharmaceutically acceptable salt thereof, and

(2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or a pharmaceutically acceptable salt thereof.

2. The combination according to claim 1 wherein the antipsychotic agent is quetiapine or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising a combination comprising:

an antipsychotic agent, or a pharmaceutically acceptable salt thereof; and

(2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or a pharmaceutically acceptable salt thereof;

together with a pharmaceutically acceptable vehicle, carrier, or diluent.

4. The pharmaceutical composition according to claim 3 wherein the antipsychotic agent is quetiapine or a pharmaceutically acceptable salt thereof.

5. A combination comprising:

an antipsychotic agent, or a pharmaceutically acceptable salt thereof; and

an α

4β

2-selective neuronal nicotinic receptor agonist, or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising a combination comprising:

antipsychotic agent, or a pharmaceutically acceptable salt thereof; and

an α

4β

2-selective neuronal nicotinic receptor agonist, or a pharmaceutically acceptable salt thereof;

together with a pharmaceutically acceptable vehicle, carrier, or diluent.

7. A kit comprising:

a dosage unit of an antipsychotic agent, or a pharmaceutically acceptable salt thereof; and

a dosage unit of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or a pharmaceutically acceptable salt thereof;

optionally with instructions for use.

8. The kit according to claim 7 wherein the antipsychotic agent is quetiapine or a pharmaceutically acceptable salt thereof.

9. A method for treating cognitive impairment and/or psychotic disorder in a subject in need thereof comprising administering simultaneously, sequentially or separately, to said subject a therapeutically effective amount of an antipsychotic agent, or a pharmaceutically acceptable salt thereof, and (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or a pharmaceutically acceptable salt thereof.

10. The method according to claim 9 whereby the psychotic disorder is selected from schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, treatment-resistant shared psychotic disorder, and psychotic disorder due to a medical condition.

11. The method according to claim 9 wherein the antipsychotic agent and (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or pharmaceutically acceptable salts thereof, are administered simultaneously, sequentially or separately, to the subject in a pharmaceutical composition additionally comprising a pharmaceutically acceptable vehicle, carrier, or diluent.

12. The method according to claim 10 wherein the antipsychotic agent and (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or pharmaceutically acceptable salts thereof, are administered simultaneously, sequentially or separately, to the subject in a pharmaceutical composition additionally comprising a pharmaceutically acceptable vehicle, carrier, or diluent.

13. The method according to claim 9 wherein the antipsychotic agent is quetiapine, or a pharmaceutically acceptable salt thereof.

14. The method according to claim 9 wherein the dose of quetiapine is between 5 and 50 mg/kg.

15. The method according to claim 9 wherein the dose of quetiapine is between 10 and 40 mg/kg.

16. The method according to claim 9 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.001 and 0.5 mg/kg.

17. The method according to claim 9 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.01 and 0.3 mg/kg.

18. A method for improving the antipsychotic effect of quetiapine in a subject in need thereof comprising administering simultaneously, sequentially or separately, to said subject an antipsychotic agent, or a pharmaceutically acceptable salt thereof, and (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or a pharmaceutically acceptable salt thereof.

19. The method according to claim 18 wherein the antipsychotic agent is quetiapine, or a pharmaceutically acceptable salt thereof.

20. The method according to claim 18 wherein the dose of quetiapine is between 5 and 50 mg/kg.

21. The method according to claim 18 wherein the dose of quetiapine is between 10 and 40 mg/kg.

22. The method according to claim 18 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.001 and 0.5 mg/kg.

23. The method according to claim 18 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.01 and 0.3 mg/kg.

24. A method of increasing dopamine release in prefrontal cortex in a subject in need thereof comprising administering simultaneously, sequentially or separately, to said subject an antipsychotic agent, or a pharmaceutically acceptable salt thereof, and (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or a pharmaceutically acceptable salt thereof.

25. The method according to claim 24 wherein the antipsychotic agent is quetiapine, or a pharmaceutically acceptable salt thereof.

26. The method according to claim 24 wherein the dose of quetiapine is between 5 and 50 mg/kg.

27. The method according to claim 24 wherein the dose of quetiapine is between 10 and 40 mg/kg.

28. The method according to claim 24 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.001 and 0.5 mg/kg.

29. The method according to claim 24 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.01 and 0.3 mg/kg.

30. A method of reducing a sedative side effect of quetiapine in a subject in need thereof comprising administering simultaneously, sequentially or separately, to said subject a therapeutically effective amount of an antipsychotic agent, or a pharmaceutically acceptable salt thereof, and (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or a pharmaceutically acceptable salt thereof.

31. The method according to claim 30 wherein the antipsychotic agent is quetiapine, or a pharmaceutically acceptable salt thereof.

32. The method according to claim 30 wherein the dose of quetiapine is between 5 and 50 mg/kg.

33. The method according to claim 30 wherein the dose of quetiapine is between 10 and 40 mg/kg.

34. The method according to claim 30 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.001 and 0.5 mg/kg.

35. The method according to claim 30 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.01 and 0.3 mg/kg.

36. A method of inhibiting acoustic startle in a subject in need thereof comprising administering simultaneously, sequentially or separately, to said subject an antipsychotic agent, or a pharmaceutically acceptable salt thereof, and (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or a pharmaceutically acceptable salt thereof.

37. The method according to claim 36 wherein the antipsychotic agent is quetiapine or a pharmaceutically acceptable salt thereof.

38. The method according to claim 36 wherein the dose of quetiapine is between 1 and 25 mg/kg.

39. The method according to claim 36 wherein the dose of quetiapine is between 5 and 20 mg/kg.

40. The method according to claim 36 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.001 and 0.05 mg/kg.

41. The method according to claim 36 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.01 and 0.03 mg/kg.

42. A method of enhancing quetiapine-mediated reduction of phencyclidine-induced disruption of prepulse inhibition in a subject in need thereof comprising administering simultaneously, sequentially or separately, to said subject an antipsychotic agent, or a pharmaceutically acceptable salt thereof, and (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or a pharmaceutically acceptable salt thereof.

43. The method according to claim 42 wherein the antipsychotic agent is quetiapine or a pharmaceutically acceptable salt thereof.

44. The method according to claim 42 wherein the dose of quetiapine is between 1 and 25 mg/kg.

45. The method according to claim 42 wherein the dose of quetiapine is between 5 and 20 mg/kg.

46. The method according to claim 42 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.001 and 0.05 mg/kg.

47. The method according to claim 42 wherein the dose of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine is between 0.01 and 0.03 mg/kg.

48. A method of reducing haloperidol-induced catalepsy in a subject in need thereof comprising administering simultaneously, sequentially or separately, to said subject haloperidol, or a pharmaceutically acceptable salt thereof, and (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, or a pharmaceutically acceptable salt thereof.

49. A method of treating cognitive impairment and psychotic disorder in a subject in need thereof comprising administering simultaneously, sequentially or separately, to said subject an amount an antipsychotic agent, or a pharmaceutically acceptable salt thereof, and an amount of an α

4β

2 selective neuronal nicotinic receptor agonist, or a pharmaceutically acceptable salt thereof.