Method of treating mental disorders using of D4 and 5-HT2A antagonists, inverse agonists or partial agonists

• US 7,884,096 B2
• Filed: 12/02/2003
• Issued: 02/08/2011
• Est. Priority Date: 12/02/2003
• Status: Expired due to Fees

• Current Assignee: Pharmaneuroboost N.V.
• Original Assignee: Pharmaneuroboost N.V.
• Inventors: Buntinx, Erik
• Primary Examiner(s): Padmanabhan; Sreeni
• Assistant Examiner(s): Ramachandran; Umamaheswari
• Application Number:
  US10/725,965
• Publication Number:
  US 20050119253A1
• Time in Patent Office: 2,625 Days
• Field of Search: 514/469, 514/217, 514/232.8, 514/317, 514/649, 549/467
• US Class Current: 514/217
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Abstract

The present invention relates to methods of treating the underlying dysregulation of the emotional functionality of mental disorders (i.e. affect instability—hypersensitivity—hyperaesthesia—dissociative phenomena—. . . ) using compounds and compositions of compounds having D4 and/or 5-HT2A antagonistic, partial agonistic or inverse agonistic activity. The invention also relates to methods comprising administering to a patient diagnosed as having a neuropsychiatric disorder a pharmaceutical composition containing (i) compounds having D4 antagonistic, partial agonistic or inverse agonistic activity and/or (ii) compounds having 5-HT2A antagonistic, partial agonistic or inverse agonistic, and/or (iii) any known medicinal compound and compositions of said compounds. The combined D4 and 5-HT2A antagonistic, partial agonistic or inverse agonistic effects may reside within the same chemical or biological compound or in two different chemical and/or biological compounds.

Claims

1. A pharmaceutical composition for treating a mood disorder or an anxiety disorder comprising:

(a) pipamperone in a dose of 5-15 mg,

(b) citalopram in a dose of 10-40 mg, and a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1 for treating a mood disorder.

3. The pharmaceutical composition of claim 1 for treating an anxiety disorder.

7. The pharmaceutical composition of claim 1 comprising pipamperone in a dose of 5 mg.

8. The pharmaceutical composition of claim 2 comprising pipamperone in a dose of 5 mg.

9. The pharmaceutical composition of claim 3 comprising pipamperone in a dose of 5 mg.

13. The pharmaceutical composition of claim 1 comprising pipamperone in a dose of 10 mg.

14. The pharmaceutical composition of claim 2 comprising pipamperone in a dose of 10 mg.

15. The pharmaceutical composition of claim 3 comprising pipamperone in a dose of 10 mg.

19. The pharmaceutical composition of claim 1 comprising pipamperone in a dose of 15 mg.

20. The pharmaceutical composition of claim 2 comprising pipamperone in a dose of 15 mg.

21. The pharmaceutical composition of claim 3 comprising pipamperone in a dose of 15 mg.

25. The pharmaceutical composition of claim 1 comprising citalopram in a dose of 10 mg.

26. The pharmaceutical composition of claim 2 comprising citalopram in a dose of 10 mg.

27. The pharmaceutical composition of claim 3 comprising citalopram in a dose of 10 mg.

31. The pharmaceutical composition of claim 1 comprising citalopram in a dose of 20 mg.

32. The pharmaceutical composition of claim 2 comprising citalopram in a dose of 20 mg.

33. The pharmaceutical composition of claim 3 comprising citalopram in a dose of 20 mg.

37. The pharmaceutical composition of claim 1 comprising citalopram in a dose of 40 mg.

38. The pharmaceutical composition of claim 2 comprising citalopram in a dose of 40 mg.

39. The pharmaceutical composition of claim 3 comprising citalopram in a dose of 40 mg.

43. The pharmaceutical composition of claim 1 comprising pipamperone in a dose of 15 mg and citalopram in a dose of 20 mg.

44. The pharmaceutical composition of claim 2 comprising pipamperone in a dose of 15 mg and citalopram in a dose of 20 mg.

45. The pharmaceutical composition of claim 3 comprising pipamperone in a dose of 15 mg and citalopram in a dose of 20 mg.

49. The pharmaceutical composition of claim 1 formulated for daily administration.

50. The pharmaceutical composition of claim 2 formulated for daily administration.

51. The pharmaceutical composition of claim 3 formulated for daily administration.

55. The pharmaceutical composition of claim 1, wherein the daily dose of pipamperone is 5-15 mg per day.

56. The pharmaceutical composition of claim 2, wherein the daily dose of pipamperone is 5-15 mg per day.

57. The pharmaceutical composition of claim 3, wherein the daily dose of pipamperone is 5-15 mg per day.

61. The pharmaceutical composition of claim 1, wherein the daily dose of pipamperone is 15 mg per day.

62. The pharmaceutical composition of claim 2, wherein the daily dose of pipamperone is 15 mg per day.

63. The pharmaceutical composition of claim 3, wherein the daily dose of pipamperone is 15 mg per day.

67. The pharmaceutical composition of claim 1, wherein the daily dose of citalopram is 10-40 mg per day.

68. The pharmaceutical composition of claim 2, wherein the daily dose of citalopram is 10-40 mg per day.

69. The pharmaceutical composition of claim 3, wherein the daily dose of citalopram is 10-40 mg per day.

73. The pharmaceutical composition of claim 1, wherein the daily dose of citalopram is 20 mg per day.

74. The pharmaceutical composition of claim 2, wherein the daily dose of citalopram is 20 mg per day.

75. The pharmaceutical composition of claim 3, wherein the daily dose of citalopram is 20 mg per day.

79. The pharmaceutical composition of claim 1, wherein the daily dose of pipamperone is 15 mg per day and the daily dose of citalopram is 20 mg per day.

80. The pharmaceutical composition of claim 2, wherein the daily dose of pipamperone is 15 mg per day and the daily dose of citalopram is 20 mg per day.

81. The pharmaceutical composition of claim 3, wherein the daily dose of pipamperone is 15 mg per day and the daily dose of citalopram is 20 mg per day.

85. The pharmaceutical composition of claim 1, wherein pipamperone is in the form of a pharmaceutically acceptable salt.

86. The pharmaceutical composition of claim 2, wherein pipamperone is in the form of a pharmaceutically acceptable salt.

87. The pharmaceutical composition of claim 3, wherein pipamperone is in the form of a pharmaceutically acceptable salt.

91. The pharmaceutical composition of claim 1, wherein citalopram is in the form of a pharmaceutically acceptable salt.

92. The pharmaceutical composition of claim 2, wherein citalopram is in the form of a pharmaceutically acceptable salt.

93. The pharmaceutical composition of claim 3, wherein citalopram is in the form of a pharmaceutically acceptable salt.

97. The pharmaceutical composition of claim 1 formulated for twice daily administration.

4. A pharmaceutical composition comprising:

(a) pipamperone in a dose of 5-15 mg,

(b) citalopram in a dose of 10-40 mg, and a pharmaceutically acceptable carrier.

5. The pharmaceutical composition of claim 4, wherein pipamperon and citalopram are present in an amount effective to treat a mood disorder.

6. The pharmaceutical composition of claim 4, wherein pipamperon and citalopram are present in an amount effective to treat an anxiety disorder.

10. The pharmaceutical composition of claim 4 comprising pipamperone in a dose of 5 mg.

11. The pharmaceutical composition of claim 5 comprising pipamperone in a dose of 5 mg.

12. The pharmaceutical composition of claim 6 comprising pipamperone in a dose of 5 mg.

16. The pharmaceutical composition of claim 4 comprising pipamperone in a dose of 10 mg.

17. The pharmaceutical composition of claim 5 comprising pipamperone in a dose of 10 mg.

18. The pharmaceutical composition of claim 6 comprising pipamperone in a dose of 10 mg.

22. The pharmaceutical composition of claim 4 comprising pipamperone in a dose of 15 mg.

23. The pharmaceutical composition of claim 5 comprising pipamperone in a dose of 15 mg.

24. The pharmaceutical composition of claim 6 comprising pipamperone in a dose of 15 mg.

28. The pharmaceutical composition of claim 4 comprising citalopram in a dose of 10 mg.

29. The pharmaceutical composition of claim 5 comprising citalopram in a dose of 10 mg.

30. The pharmaceutical composition of claim 6 comprising citalopram in a dose of 10 mg.

34. The pharmaceutical composition of claim 4 comprising citalopram in a dose of 20 mg.

35. The pharmaceutical composition of claim 5 comprising citalopram in a dose of 20 mg.

36. The pharmaceutical composition of claim 6 comprising citalopram in a dose of 20 mg.

40. The pharmaceutical composition of claim 4 comprising citalopram in a dose of 40 mg.

41. The pharmaceutical composition of claim 5 comprising citalopram in a dose of 40 mg.

42. The pharmaceutical composition of claim 6 comprising citalopram in a dose of 40 mg.

46. The pharmaceutical composition of claim 4 comprising pipamperone in a dose of 15 mg and citalopram in a dose of 20 mg.

47. The pharmaceutical composition of claim 5 comprising pipamperone in a dose of 15 mg and citalopram in a dose of 20 mg.

48. The pharmaceutical composition of claim 6 comprising pipamperone in a dose of 15 mg and citalopram in a dose of 20 mg.

52. The pharmaceutical composition of claim 4 formulated for daily administration.

53. The pharmaceutical composition of claim 5 formulated for daily administration.

54. The pharmaceutical composition of claim 6 formulated for daily administration.

58. The pharmaceutical composition of claim 4, wherein the daily dose of pipamperone is 5-15 mg per day.

59. The pharmaceutical composition of claim 5, wherein the daily dose of pipamperone is 5-15 mg per day.

60. The pharmaceutical composition of claim 6, wherein the daily dose of pipamperone is 5-15 mg per day.

64. The pharmaceutical composition of claim 4, wherein the daily dose of pipamperone is 15 mg per day.

65. The pharmaceutical composition of claim 5, wherein the daily dose of pipamperone is 15 mg per day.

66. The pharmaceutical composition of claim 6, wherein the daily dose of pipamperone is 15 mg per day.

70. The pharmaceutical composition of claim 4, wherein the daily dose of citalopram is 10-40 mg per day.

71. The pharmaceutical composition of claim 5, wherein the daily dose of citalopram is 10-40 mg per day.

72. The pharmaceutical composition of claim 6, wherein the daily dose of citalopram is 10-40 mg per day.

76. The pharmaceutical composition of claim 4, wherein the daily dose of citalopram is 20 mg per day.

77. The pharmaceutical composition of claim 5, wherein the daily dose of citalopram is 20 mg per day.

78. The pharmaceutical composition of claim 6, wherein the daily dose of citalopram is 20 mg per day.

82. The pharmaceutical composition of claim 4, wherein the daily dose of pipamperone is 15 mg per day and the daily dose of citalopram is 20 mg per day.

83. The pharmaceutical composition of claim 5, wherein the daily dose of pipamperone is 15 mg per day and the daily dose of citalopram is 20 mg per day.

84. The pharmaceutical composition of claim 6, wherein the daily dose of pipamperone is 15 mg per day and the daily dose of citalopram is 20 mg per day.

88. The pharmaceutical composition of claim 4, wherein pipamperone is in the form of a pharmaceutically acceptable salt.

89. The pharmaceutical composition of claim 5, wherein pipamperone is in the form of a pharmaceutically acceptable salt.

90. The pharmaceutical composition of claim 6, wherein pipamperone is in the form of a pharmaceutically acceptable salt.

94. The pharmaceutical composition of claim 4, wherein citalopram is in the form of a pharmaceutically acceptable salt.

95. The pharmaceutical composition of claim 5, wherein citalopram is in the form of a pharmaceutically acceptable salt.

96. The pharmaceutical composition of claim 6, wherein citalopram is in the form of a pharmaceutically acceptable salt.

98. The pharmaceutical composition of claim 4 formulated for twice daily administration.