Selective serotonin receptor inverse agonists as therapeutics for disease

• US 7,863,296 B2
• Filed: 05/20/2005
• Issued: 01/04/2011
• Est. Priority Date: 05/21/2004
• Status: Active Grant

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: Nash, Norman, Davis, Robert E., Brann, Mark R., Weiner, David M.
• Primary Examiner(s): Padmanabhan; Sreeni
• Assistant Examiner(s): Javanmard; Sahar
• Application Number:
  US11/134,769
• Publication Number:
  US 20050288328A1
• Time in Patent Office: 2,055 Days
• Field of Search: 514/277, 514/317
• 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 compound of Formula (I)

2. The pharmaceutical composition of claim 1, wherein the anti-insomnia drug is an H1 antagonist or inverse agonist.

3. The pharmaceutical composition of claim 2, 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, ketotifen, levocabastine, meclizine, mepramine, mianserin, promethazine, tripelennamine, triprolidine, acrivastine, cetirizine, desloratadine, fexofenadine, and loratadine.

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

5. The pharmaceutical composition of claim 1, wherein the anti-insomnia drug is selected from the group consisting of alprazolam (XANAX), chlordiazepoxide (LIBRIUM, LIMBITROL), clorazepate (TRANXENE), estazolam (PROSOM), flurazepam (DALMANE), hydroxyzine (ATARAX), lorazepam (ATIVAN), pentobarbital (NEMBUTAL), quazepam (DORAL), secobarbital (SECONAL), temazepam (RESTORIL), triazolam (HALCION), valium, zaleplon (SONATA), zolpidem (AMBIEN), and the benzodiazepine family of drugs.

6. The pharmaceutical composition of claim 1, wherein the anti-insomnia drug is a non-benzodiazepine hypnotic selected from the group consisting of zolpidem, zopiclone, eszopiclone, zaleplon, gaboxadol, indiplon, and abecarnil.

7. The pharmaceutical composition of claim 1, wherein the anti-insomnia drug is a sleep inducing agent.

8. The pharmaceutical composition of claim 7, wherein the sleep inducing agent is selected from the group consisting of a barbiturate, a benzodiazepine, a direct GABA agonist, a positive allosteric modulator of GABA receptors, a histamine receptor antagonist, and a histamine receptor inverse agonist.

9. The composition of claim 1, wherein the compound of formula (I) is the free base.

10. The composition of claim 1, wherein the compound of formula (I) is the tartrate salt.

11. The composition of claim 1, wherein the compound of formula (I) is the hydrochloride salt.

12. The composition of claim 1, wherein the composition is in a single unit dosage form.

13. The composition of claim 12, wherein the composition is in a single unit dosage form suitable for oral administration to a human.

14. The composition of claim 12, wherein the dosage form is solid.

15. The composition of claim 12, wherein the composition is in the form of a tablet or a capsule.

16. The composition of claim 12, wherein the composition is in the form of a tablet.

17. The composition of claim 1, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is from about 0.1 mg to about 500 mg.

18. The composition of claim 1, wherein the amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, is from about 1 mg to about 40 mg.