Methods of identifying inverse agonists of the serotonin 2A receptor

• US 6,358,698 B1
• Filed: 10/06/1999
• Issued: 03/19/2002
• Est. Priority Date: 10/07/1998
• Status: Expired due to Term

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: Brann, Mark R., Weiner, David
• Primary Examiner(s): ULM, JOHN D
• Application Number:
  US09/413,626
• Time in Patent Office: 895 Days
• Field of Search: 435/7.1, 435/7.2, 435/7.21, 436/501
• US Class Current: 435/7.21
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/70571 for neuromediators, e.g. serotonin receptor, dopamine receptor
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 2800/304 Mood disorders, e.g. bipolar, depression
• CPC Class Codes: G01N 33/566 using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

The present invention relates to a method of identifying compounds which act as inverse agonists of the 5-HT2A receptor, the method comprising contacting a constitutively active 5-HT2A receptor with at least one test compound and determining any decrease in the level of basal activity of the receptor so as to identify a test compound which is an inverse agonist of the 5-HT2A receptor. Such inverse agonists may be used in the treatment of schizophrenia and related psychoses.

Claims

1. A method of identifying a compound with antipsychotic activity, the method comprising:

(a) contacting a 5-HT2A receptor having wild type constitutive activity with at least one test compound; and

(b) determining any decrease in basal activity of the 5-HT2A receptor having wild type constitutive activity, wherein a decrease in basal activity of the 5-HT2A receptor identifies a compound with antipsychotic activity.

2. The method of claim 1, wherein the 5-HT2A receptor is human.

3. A method of identifying a compound with antipsychotic activity, the method comprising:

(a) culturing cells which express a 5-HT2A receptor having wild type constitutive activity;

(b) incubating the cells with at least one test compound; and

(c) determining any decrease in basal activity of the 5-HT2A receptor having wild type constitutive activity, wherein a decrease in basal activity of the 5-HT2A receptor identifies a compound with antipsychotic activity.

4. The method of claim 3, wherein the 5-HT2A receptor is human.

5. The method of claim 3, wherein the cells of step (a) overexpress said 5-HT2A receptor.

6. The method of claim 3, wherein the identified antipsychotic compound is selective for the 5-HT2A receptor.

7. A method of identifying a compound useful in treating the symptoms of disease or disorder associated with constitutive activity of the 5-HTA receptor, the method comprising:

(a) contacting a 5-HT2A receptor having wild type constitutive activity with at least one test compound; and

(b) determining any decrease in basal activity of the 5-HT2A receptor having wild type constitutive activity, wherein a decrease in basal activity of the 5-HT2A receptor identifies a compound useful in treating the symptoms of disease or disorder associated with constitutive activity of the 5-HTA receptor.

8. The method of claim 7, wherein the 5-HT2A receptor is human.

9. The method of claim 7, wherein the disease or disorder is psychosis.

10. The method of claim 7, wherein the disease or disorder is schizophrenia.

11. The method of claim 7, wherein said symptoms are selected from the group consisting of:

hallucination, delusion, emotional withdrawal, apathy and poverty of speech.