Use of N-desmethylclozapine to treat human neuropsychiatric disease

• US 20050085463A1
• Filed: 08/05/2004
• Published: 04/21/2005
• 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:
  US10/913,117
• Publication Number:
  US 20050085463A1
• Time in Patent Office: Days
• US Class Current: 514/220
• 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 treating cognitive impairment comprising:

identifying a subject in need of improvement of cognition; and

administering an amount of N-desmethylclozapine to said subject which is thereapeutically effective in improving the cognition of said subject.

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 monoamine reputkate inhibitiors, selective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, dual serotonin and norepinephrine reupake inhibitors, dopamine agonists, antipsychotic agents, inverse serotonin agonists, serotonin antagonists, serotonin 2 inverse agonists, serotonin 2 antagonists, serotonin1A agonists, antiepileptic and peripherally acting muscarinic antagonists.

10. The method of claim 1, wherein said subject suffers from a condition selected from the group consisting of hallucinations, delusions, disordered thought, behavioral disturbance, aggression, suicidality, mania, anhedonia, flattening of affect, affective disorders, depression, mania, dementia, neuropathic pain, glaucoma and two or more any of the foregoing conditions.

11. A method of activating an M1 muscarinic receptor comprising contacting said receptor with N-desmethylclozapine.

12. A method of ameliorating at least one symptom of a condition where it is beneficial to increase the level of activity of an M1 muscarinic receptor comprising:

determining that a subject would benefit from an increased level of activity of an M1 muscarinic receptor; and

administering an amount of N-desmethylclozapine which is therapeutically effective to increase the level of activity of said M1 muscarinic receptor and to ameliorate said at least one symptom to said subject.

13. The method of claim 12, wherein the subject is human.

14. The method of claim 12, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a single dose.

15. The method of claim 12, wherein the therapeutically effective amount of N-desmethylclozapine is administered as a plurality of doses.

16. The method of claim 12, further comprising contacting said subject with 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. The method of claim 12, wherein said subject suffers from a condition selected from the group consisting of hallucinations, delusions, disordered thought, behavioral disturbance, aggression, suicidality, mania, anhedonia, flattening of affect, affective disorders, depression, mania, dementia, neuropathic pain, glaucoma and two or more any of the foregoing conditions.