Selective serotonin receptor inverse agonists as therapeutics for disease

• US 20050288328A1
• Filed: 05/20/2005
• Published: 12/29/2005
• Est. Priority Date: 05/21/2004
• Status: Active Grant

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: Davis, Robert E., Brann, Mark R., Weiner, David M.
• Granted Patent: US 7,863,296 B2
• Time in Patent Office: Days
• US Class Current: 514/317
• 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 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Disclosed herein are pharmaceutical compositions comprising an inverse serotonin receptor agonist or a serotonin receptor antagonist and an anti-insomnia agent. Disclosed herein are also methods of treating insomnia using the disclosed pharmaceutical compositions.

Claims

1. A pharmaceutical composition comprising:

a first compound selected from the group consisting of an inverse agonist of a serotonin receptor, an antagonist of a serotonin receptor, and pharmaceutically acceptable salts thereof; and

a second compound selected from the group consisting of an anti-insomnia drug

and pharmaceutically acceptable salts thereof.

2. The pharmaceutical composition of claim 1, wherein the serotonin receptor is a 5HT2A receptor.

3. The pharmaceutical composition of claim 2, wherein the first compound is a compound of Formula (I):

4. The pharmaceutical composition of claim 2, wherein the first compound is a compound of Formula (II):

5. The pharmaceutical composition of any one of claims 1, 2, 3 or 4, wherein the anti-insomnia drug is an H1 antagonist or inverse agonist.

6. The pharmaceutical composition of claim 5, wherein the H1 antagonist or inverse agonist is selected from the group consisting of azatadine, astemizole, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, dimenhydrinate, diphenhydramine, doxepin, doxylamine, ktotifen, leocabastine, meclizine, mepramine, manserin, promethazine, tipelennamine, triprolidine, acrivastine, cetrizine, desloratadine, fexofenadine, and loratidine.

7. The pharmaceutical composition of claim 1, further comprising a physiologically acceptable carrier, diluent, excipient, or combination thereof.

8. A method of treating insomnia in a patient, comprising:

identifying a patient in need of such treatment, and

administering to said patient a therapeutically effective amount of a combination of a first compound and a second compound, the first compound selected from the group consisting of an inverse agonist of a serotonin receptor, an antagonist of a serotonin receptor, and

pharmaceutically acceptable salts thereof, the second compound selected from the group consisting of an anti-insomnia drug and pharmaceutically acceptable salts thereof.

9. The method of claim 8, wherein the serotonin receptor is a 5HT2A receptor.

10. The method of claim 9, wherein the first compound is a compound of Formula

11. The method of claim 9, wherein the first compound is a compound of Formula (II):

12. The method of claim any one of claims 8, 9, 10 or 11, wherein the anti-insomnia drug is an H1 antagonist or inverse agonist.

13. The method of claim 12, wherein the H1 antagonist or inverse agonistis selected from the group consisting of azatadine, astemizole, brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, dimenhydrinate, diphenhydramine, doxepin, doxylamine, ktotifen, leocabastine, meclizine, mepramine, manserin, promethazine, tipelennamine, triprolidine, acrivastine, cetrizine, desloratadine, fexofenadine, and loratidine.