Use of N-desmethylclozapine to treat human neuropsychiatric disease

• US 20050250767A1
• Filed: 04/04/2005
• Published: 11/10/2005
• 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:
  US11/098,892
• Publication Number:
  US 20050250767A1
• Time in Patent Office: Days
• US Class Current: 514/225.800
• CPC Class Codes: A61K 31/4743 condensed with ring systems having sulfur as a ring hetero atom
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine

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 ameliorating one or more symptoms of psychosis, comprising administering to a subject exhibiting one or more symptoms of psychosis a therapeutically effective amount of N-desmethylclozapine essentially free of clozapine.

2. The method of claim 1, further comprising identifying a subject exhibiting one or more symptoms of psychosis.

3. The method of claim 1, wherein the psychosis is induced by exposure of the subject to one or more medications.

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

5. The method of claim 1, wherein the N-desmethylclozapine is administered as a single daily dose or administered in divided doses.

6. The method of claim 1, wherein the N-desmethylclozapine is administered two, three or four times daily.

7. A method of ameliorating one or more symptoms of an affective disorder, comprising administering to a subject exhibiting one or more symptoms of an affective disorder a therapeutically effective amount of N-desmethylclozapine essentially free of clozapine.

8. The method of claim 7, further comprising identifying a subject exhibiting one or more symptoms of an affective disorder.

9. The method of claim 7, wherein the affective disorder is depression.

10. The method of claim 7, wherein the affective disorder is mania.

11. A method of ameliorating one or more symptoms of dementia, comprising administering to a subject exhibiting one or more symptoms of dementia a therapeutically effective amount of N-desmethylclozapine essentially free of clozapine.

12. The method of claim 11, further comprising identifying a subject exhibiting one or more symptoms of dementia.

13. The method of claim 11, wherein the dementia comprises cognitive impairment.

14. The method of claim 11, wherein the dementia comprises behavioral disturbances.

15. A method of ameliorating one or more symptoms of neuropathic pain, comprising administering to a subject exhibiting one or more symptoms of neuropathic pain a therapeutically effective amount of N-desmethylclozapine essentially free of clozapine.

16. The method of claim 15, further comprising identifying a subject exhibiting one or more symptoms of neuropathic pain.

17. A method of ameliorating one or more symptoms of glaucoma, comprising administering to a subject exhibiting one or more symptoms of glaucoma a therapeutically effective amount of N-desmethylclozapine essentially free of clozapine.

18. The method of claim 17, further comprising identifying a subject exhibiting one or more symptoms of glaucoma.

19. A method of ameliorating one or more symptoms of psychosis, comprising administering to a subject N-desmethylclozapine in combination with another anti-psychotic agent, wherein at least a portion of the N-desmethylclozapine is administered by directly introducing N-desmethylclozapine to the subject.

20. The method of claim 19, wherein directly introducing N-desmethylclozapine to the subject comprises orally administering N-desmethylclozapine.

21. The method of claim 19, wherein directly introducing N-desmethylclozapine to the subject comprises intravenous injection of N-desmethylclozapine.

22. The method of claim 19, wherein the other anti-psychotic agent is selected from the group consisting of a phenothiazine, phenylbutylpiperadine, debenzapine, benzisoxidil, and a salt of lithium.

23. The method of claim 22, wherein the phenothiazine is selected from the group consisting of chlorpromazine (Thorazine(®

), mesoridazine (Serentil(®

), prochlorperazine (Compazine®

), and thioridazine (Mellaril®

).

24. The method of claim 22, wherein the phenylbutylpiperadine is selected from the group consisting of haloperidol (Haldol®

) and pimozide (Orap®

).

25. The method of claim 22, wherein the debenzapine is selected from the group consisting of clozapine (Clozaril®

), loxapine (Loxitane®

), olanzapine (Zyprexa®

) and quetiapine (Seroquel®

).

26. The method of claim 22, wherein the benzisoxidil is selected from the group consisting of resperidone (Resperidal®

) and ziprasidone (Geodon®

).

27. The method of claim 22, wherein the salt of lithium is lithium carbonate.

28. The method of claim 19, wherein the antipsychotic agent is selected from the group consisting of 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, and Zyprexa, or pharmaceutically acceptable salts thereof.

29. A method of ameliorating one or more symptoms of psychosis, comprising administering to a subject exhibiting one or more symptoms of psychosis a therapeutically effective amount of a pharmaceutical composition comprising N-desmethylclozapine and a pharmaceutically acceptable excipient or diluent, wherein the amount of any clozapine administered is low enough such that the combined N-desmethylclozapine and clozapine result in a net agonism at muscarinic receptors.

30. A method of ameliorating one or more symptoms of an affective disorder, comprising administering to a subject exhibiting one or more symptoms of an affective disorder a therapeutically effective amount of a pharmaceutical composition comprising N-desmethylclozapine and a pharmaceutically acceptable excipient or diluent, wherein the amount of any clozapine administered is low enough such that the combined N-desmethylclozapine and clozapine result in a net agonism at muscarinic receptors.

31. A method of ameliorating one or more symptoms of dementia, comprising administering to a subject exhibiting one or more symptoms of dementia a therapeutically effective amount of a pharmaceutical composition comprising N-desmethylclozapine and a pharmaceutically acceptable excipient or diluent, wherein the amount of any clozapine administered is low enough such that the combined N-desmethylclozapine and clozapine result in a net agonism at muscarinic receptors.

32. A method of ameliorating one or more symptoms of neuropathic pain, comprising administering to a subject exhibiting one or more symptoms of neuropathic pain a therapeutically effective amount of a pharmaceutical composition comprising N-desmethylclozapine and a pharmaceutically acceptable excipient or diluent, wherein the amount of any clozapine administered is low enough such that the combined N-desmethylclozapine and clozapine result in a net agonism at muscarinic receptors.

33. A method of ameliorating one or more symptoms of glaucoma, comprising administering to a subject exhibiting one or more symptoms of glaucoma a therapeutically effective amount of a pharmaceutical composition comprising N-desmethylclozapine and a pharmaceutically acceptable excipient or diluent, wherein the amount of any clozapine administered is low enough such that the combined N-desmethylclozapine and clozapine result in a net agonism at muscarinic receptors.