Anti-psychosis combination

• US 20020156068A1
• Filed: 03/22/2002
• Published: 10/24/2002
• Est. Priority Date: 03/22/2001
• Status: Abandoned Application

• Current Assignee: Arena Pharmaceuticals Incorporated (Pfizer Inc.)
• Original Assignee: Arena Pharmaceuticals Incorporated (Pfizer Inc.)
• Inventors: Chalmers, Derek T., Behan, Dominic P.
• Application Number:
  US10/104,602
• Publication Number:
  US 20020156068A1
• Time in Patent Office: Days
• US Class Current: 514/220
• 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 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• 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

Abstract

This invention relates to methods of reducing hyperlocomotor activity and stereotypy by administering a composition comprising a modulator of the 5-HT2A receptor with a neuroleptic agent used for treating psychoses, such as Haloperidol. The invention further relates to compositions comprising a modulator of the 5-HT2A receptor with a neuroleptic agent.

Claims

1. A composition comprising a neuroleptic and a modulator of a 5-HT2A receptor.

2. The composition of claim 1 wherein the neuroleptic is selected from the group consisting of Haloperidol, Haloperidol decanoate, Clozapine, Benperidol;

Chlorpromazine, Droperidol, Flupenthixol, Flupenthixol decanoate, Fluspiriline, Methotrimeprazine, Levomepromazine, Olanzapine, Oxypertine, Pericyazine, Perphenazine, Pimozide, Pipothiazine decanoate, Prochlorperazine, Promazine, Quetiapine, Remoxipride, Risperidone, Sertindole, Sulpiride, Thioridazine, Trifluoperazine, Zucopenthixol decanoate, Zuclopenthixol, and Clopixol.

3. The composition of claim 2 wherein the neuroleptic is Haloperidol.

4. The composition of claim 1 wherein the modulator of the 5-HT2A receptor is an inverse agonist of the 5-HT2A receptor.

5. The composition of claim 4 wherein the inverse agonist of the 5-HT2A receptor is N-[3-(4-bromo-2-methylpyrazol-3-yl)phenyl][(4-chlorophenyl)amino]carboxamide, or a derivative thereof.

6. The composition of claim 5 wherein the neuroleptic is Haloperidol.

8. The composition of claim 6 wherein the compound of formula A has the formula:

9. The composition of claim 8 wherein the neuroleptic is selected from the group consisting of Haloperidol, Haloperidol decanoate, Clozapine, Benperidol;

Chlorpromazine, Droperidol, Flupenthixol, Flupenthixol decanoate, Fluspiriline, Methotrimeprazine, Levomepromazine, Olanzapine, Oxypertine, Pericyazine, Perphenazine, Pimozide, Pipothiazine decanoate, Prochlorperazine, Promazine, Quetiapine, Remoxipride, Risperidone, Sertindole, Sulpiride, Thioridazine, Trifluoperazine, Zucopenthixol decanoate, Zuclopenthixol, and Clopixol.

10. The composition of claim 9 wherein the neuroleptic is Haloperidol.

11. A method of reducing hyperlocomotor activity comprising administering to a subject a pharmaceutically effective amount of the composition of claim 1.

12. The method of claim 11 wherein the modulator of the 5HT-2A receptor is a compound of formula A having the formula:

13. The method of claim 11 wherein the neuroleptic is Haloperidol and the modulator of the 5HT-2A receptor has the formula:

14. A method of reducing stereotypy comprising administering to a subject a pharmaceutically effective amount of the composition of claim 1.

15. The method of claim 14 wherein the modulator of the 5HT-2A receptor is a compound of formula A having the formula:

16. The method of claim 15 wherein the neuroleptic is Haloperidol and the modulator of the 5HT-2A receptor has the formula:

17. A method of treating psychoses in a mammal while minimizing motor-related side effects comprising administering to a subject a pharmaceutically effective amount of the composition of claim 1.

18. The method of claim 17 wherein the modulator of the 5HT-2A receptor is a compound of formula A having the formula:

19. The method of claim 17 wherein the neuroleptic is Haloperidol and the modulator of the 5HT-2A receptor has the formula:

20. A method of treating psychoses in a subject while minimizing extrapyramidal motor syndrome comprising administering to a subject a pharmaceutically effective amount of the composition of claim 1.

21. The method of claim 20 wherein the modulator of the 5HT-2A receptor is a compound of formula A having the formula:

22. The method of claim 20 wherein the neuroleptic is Haloperidol and the modulator of the 5HT-2A receptor has the formula:

23. The method of any one of claims 11, 13, 14, 16, 17, 19 or 20 further comprising the step of identifying a subject, said subject being in need of treatment of a psychosis susceptible to undesired side effects, wherein said identifying step is performed prior to administering to said subject said pharmaceutically effective amount of said composition.

7. A composition comprising a neuroleptic and a compound having the formula A: