Use of N-desmethylclozapine to treat human neuropsychiatric disease

• US 20040224942A1
• Filed: 01/21/2004
• Published: 11/11/2004
• Est. Priority Date: 01/23/2003
• Status: Abandoned Application

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: Brann, Mark R., Weiner, David M.
• Application Number:
  US10/761,787
• Publication Number:
  US 20040224942A1
• Time in Patent Office: Days
• US Class Current: 514/220
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Disclosed herein is a method to treat neuropsychiatric diseases including psychosis, affective disorders, dementia, neuropathic pain, and glaucoma. Treatment is carried out by administering a therapeutically effective amount of N-desmethylclozapine to a patient suffering from a neuropsychiatric disease.

Claims

1. A method of treating psychosis comprising:

identifying a subject suffering from one or more symptoms of psychosis;

contacting said subject with a therapeutically effective amount of N-desmethylclozapine;

whereby the one or more symptoms of psychosis are ameliorated.

2. The method of claim 1, wherein the subject is human.

3. The method of claim 1, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a single dose.

4. The method of claim 1, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a plurality of doses.

5. The method of claim 1, further comprising contacting said subject with an additional therapeutic agent.

6. The method of claim 5, wherein said subject is contacted with said additional therapeutic agent subsequent to said contacting with N-desmethylclozapine.

7. The method of claim 5, wherein said subject is contacted with said additional therapeutic agent prior to said contacting with N-desmethylclozapine.

8. The method of claim 5, wherein said subject is contacted with said additional therapeutic agent substantially simultaneously with N-desmethylclozapine.

9. The method of claim 5, wherein said additional therapeutic agent is selected from the group consisting of selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, dopamine agonists, antipsychotic agents, and inverse serotonin 2A agonists.

10. A method of treating affective disorders comprising:

identifying a subject suffering from one or more symptoms of an affective disorder;

administering a therapeutically effective amount of N-desmethylclozapine to said subject, whereby the one or more symptoms of the affective disorder are ameliorated.

11. The method of claim 10, wherein the subject is human.

12. The method of claim 10, wherein the affective disorder is depression.

13. The method of claim 10, wherein the affective disorder is mania.

14. The method of claim 10, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a single dose.

15. The method of claim 10, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a plurality of doses.

16. The method of claim 10, further comprising administering to said subject an additional therapeutic agent.

17. The method of claim 16, wherein said subject is contacted with said additional therapeutic agent subsequent to said contacting with N-desmethylclozapine.

18. The method of claim 16, wherein said subject is contacted with said additional therapeutic agent prior to said contacting with N-desmethylclozapine.

19. The method of claim 16, wherein said subject is contacted with said additional therapeutic agent substantially simultaneously with N-desmethylclozapine.

20. The method of claim 16, wherein said additional therapeutic agent is selected from the group consisting of selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, dopamine agonists, antipsychotic agents, and inverse serotonin 2A agonists.

21. A method of treating dementia, comprising:

identifying a subject suffering from one or more symptoms of dementia;

administering a therapeutically effective amount of N-desmethylclozapine to said subject, whereby a desired clinical effect is produced.

22. The method of claim 21, wherein the subject is human.

23. The method of claim 21, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a single dose.

24. The method of claim 21, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a plurality of doses.

25. The method of claim 21, wherein the dementia manifests as a cognitive impairment.

26. The method of claim 21, wherein the dementia manifests as a behavioral disturbance.

27. The method of claim 21, further comprising administering to said subject an additional therapeutic agent.

28. The method of claim 27, wherein said subject is contacted with said additional therapeutic agent subsequent to said contacting with N-desmethylclozapine.

29. The method of claim 27, wherein said subject is contacted with said additional therapeutic agent prior to said contacting with N-desmethylclozapine.

30. The method of claim 27, wherein said subject is contacted with said additional therapeutic agent substantially simultaneously with N-desmethylclozapine.

31. The method of claim 27, wherein said additional therapeutic agent is selected from the group consisting of selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, dopamine agonists, antipsychotic agents, and inverse serotonin 2A agonists.

32. A method of treating neuropathic pain comprising:

identifying a subject suffering from one or more symptoms of neuropathic pain;

contacting said subject with a therapeutically effective amount of N-desmethylclozapien, whereby the symptoms of neuropathic pain are reduced.

33. The method of claim 32, wherein the subject is human.

34. The method of claim 32, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a single dose.

35. The method of claim 32, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a plurality of doses.

36. The method of claim 32, further comprising contacting said subject with an additional therapeutic agent.

37. The method of claim 36, wherein said subject is contacted with said additional therapeutic agent subsequent to said contacting with N-desmethylclozapine.

38. The method of claim 36, wherein said subject is contacted with said additional therapeutic agent prior to said contacting with N-desmethylclozapine.

39. The method of claim 36, wherein said subject is contacted with said additional therapeutic agent substantially simultaneously with N-desmethylclozapine.

40. The method of claim 36, wherein said additional therapeutic agent is selected from the group consisting of selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, dopamine agonists, antipsychotic agents, and inverse serotonin 2A agonists.

41. A method of treating glaucoma comprising:

identifying a subject suffering from one or more symptoms of glaucoma;

contacting said subject with a therapeutically effective amount of N-desmethylclozapine, whereby the symptoms of glaucoma are reduced.

42. The method of claim 41, wherein the subject is human.

43. The method of claim 41, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a single dose.

44. The method of claim 41, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a plurality of doses.

45. The method of claim 41, wherein the symptoms of glaucoma are selected from the group consisting of elevated intraocular pressure, optic nerve damage, and decreased field of vision.

46. The method of claim 41, further comprising contacting said subject with an additional therapeutic agent.

47. The method of claim 46, wherein said subject is contacted with said additional therapeutic agent subsequent to said contacting with N-desmethylclozapine.

48. The method of claim 46, wherein said subject is contacted with said additional therapeutic agent prior to said contacting with N-desmethylclozapine.

49. The method of claim 46, wherein said subject is contacted with said additional therapeutic agent substantially simultaneously with N-desmethylclozapine.

50. The method of claim 46, wherein said additional therapeutic agent is selected from the group consisting of selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, dopamine agonists, antipsychotic agents, and inverse serotonin 2A agonists.

51. A pharmaceutical composition comprising a pharmaceutically effective amount of N-desmethylclozapine and an additional therapeutic agent.

52. The composition of claim 51 wherein said additional therapeutic agent is selected from the group consisting of selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, dopamine agonists, antipsychotic agents, and inverse serotonin 2A agonists.

53. The composition of claim 52 wherein the antipsychotic agent is selected from the group consisting of a phenothiazine, phenylbutylpiperadine, debenzapine, benzisoxidil, and salt of lithium.

54. The composition of claim 52, wherein the antipsychotic agent is selected from the group consisting of chlorpromazine (Thorazine®

), mesoridazine (Serentil®

), prochlorperazine (Compazine®

), thioridazine (Mellaril®

), haloperidol (Haldol®

), pimozide (Orap®

), clozapine (Clozaril®

), loxapine (Loxitane(®

), olanzapine (Zyprexa®

), quetiapine (Seroquel®

), resperidone (Resperidal®

), ziprasidone (Geodon®

), lithium carbonate, Aripiprazole (Abilify), Clozapine, Clozaril, Compazine, Etrafon, Geodon, Haldol, Inapsine, Loxitane, Mellaril, Moban, Navane, Olanzapine (Zyprexa), Orap, Permitil, Prolixin, Phenergan, Quetiapine (Seroquel), Reglan, Risperdal, Serentil, Seroquel, Stelazine, Taractan, Thorazine, Triavil, Trilafon, Zyprexa, and pharmaceutically acceptable salts thereof.

55. The composition of claim 52, wherein the selective serotonin reuptake inhibitor is selected from the group consisting of fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, escitalopram, sibutramine, duloxetine, venlafaxine, and pharmaceutically acceptable salts and prodrugs thereof.

56. The composition of claim 52, wherein the norepinephrine reuptake inhibitor is selected from the group consisting of thionisoxetine and reboxetine.

57. The composition of claim 52, wherein the dopamine agonist is selected from the group consisting of sumatriptan, almotriptan, naratriptan, frovatriptan, rizatriptan, zomitriptan, cabergoline, amantadine, lisuride, pergolide, ropinirole, pramipexole, and bromocriptine.

58. The composition of claim 52, wherein the inverse serotonin 2A agonist is N-(1-methylpiperidin-4-flourophenylmethyl)-N'"'"'-(4-(2-methylpropyloxy)phenylmethyl)carbamide.