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

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.

What is claimed:  
     
         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.  
     
     
         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 selective inhibitors of system ASC, including alanine.  
     
     
         4 . The assay method of  claim 1  where a non-radioactive label is used.  
     
     
         5 . The assay method of  claim 3  where a selective ligand of the alanine-insensitive transport system is used in place of alanine.  
     
     
         6 . A process for augmentation of N-methyl-D-aspartate receptor-mediated neurotransmission in vivo which comprises administration of an effective amount of a D-serine transport inhibitor.  
     
     
         7 . The process of  claim 6  wherein a psychotic disorder associated with decreased N-methyl-D-aspartate receptor-mediated neurotransmission is treated.  
     
     
         8 . The process of  claim 7  wherein schizophrenia is treated.  
     
     
         9 . The process of  claim 7  wherein a neuropsychiatric disorder selected from Alzheimer's disease, bipolar illness, depression and an anxiety disorder is treated.