Assay for D-serine transport antagonist and use for treating psychosis

• US 6,361,957 B1
• Filed: 08/03/1999
• Issued: 03/26/2002
• Est. Priority Date: 08/03/1999
• Status: Expired due to Fees

• Current Assignee: Daniel Javitt
• Original Assignee: GlyTech, Inc.
• Inventors: Javitt, Daniel C.
• Primary Examiner(s): Ponnaluri, Padmashri
• Application Number:
  US09/365,889
• Time in Patent Office: 966 Days
• Field of Search: 514/42, 514/45, 514/561, 514/551, 514/578, 514/49, 514/458, 514/474, 514/554, 514/663, 514/762, 514/563, 436/501, 436/503, 436/504, 435/4, 435/7.1, 435/7.2
• US Class Current: 435/7.1
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: G01N 33/5082 Supracellular entities, e.g. tissue, organisms

Abstract

Determination of a synaptosomal D-serine transporter and use of an assay method for discovering inhibitors thereof to be used in the treatment of psychotic disorders.

Claims

1. An assay method for identifying antagonists of non-system ASC-mediated D-serine-transport comprising incubating synaptically derived brain membrane fragments (“

synaptosomes”

) with labelled D- or L-serine and with a chemical to be tested as a D-Serine transport antagonist and thereafter measuring the D- or L-Serine uptake in comparison with a control “

wherein a decrease in labeled D- or L-serine uptake in the presence of the chemical to be tested in comparison with the control identifies the chemical as a potential non-system ASC transport antagonist”

.

2. The assay method of claim 1 wherein the D- or L-Serine is radioactively labelled.

3. The assay method of claim 1 wherein the incubation is conducted in the presence of a selective inhibitor of system ASC.

4. The assay method of claim 1 wherein the D-or-L-serine are labeled with radioactive label.

5. The assay method of claim 3 wherein the selective inhibitor is alanine.

6. An assay method for identifying antagonists of non-system ASC-mediated D-serine-transport comprising incubating synaptically derived brain membrane fragments (“

synaptosomes”

) with a labeled substrate for the non-system ASC transport system and with a chemical to be tested as a D-serine transport antagonist and thereafter measuring the substrate uptake in comparison with a control “

wherein a decrease in substrate uptake in the presence of the chemical to be tested in comparison with the control identifies the chemical as a potential non-system ASC transport antagonist”

.

7. The assay method of claim 6 wherein the incubation is conducted in the presence of a selective inhibitor of system ASC.

8. The assay method of claim 7 wherein the selective inhibitor is alanine.