D-serine transport antagonist for treating psychosis

Abstract

Method and composition for augmenting NMDA receptor mediated neurotransmission involving use of a D-serine transport inhibitor.

1 - 26 . (canceled)  
     
     
         27 . A D-serine transport inhibitor compound comprising a serine or alanine compound having a hydrophobic group linked to either the C-or N-terminus, wherein the hydrophobic group is selected from the group consisting of a C1-13 alkyl group optionally substituted with a halogen atom, a phenyl group optionally substituted with a C1-13 alkyl group, a cyano group and a halogen atom.  
     
     
         28 . The D-serine transport inhibitor compound according to  claim 27 , wherein the serine or alanine compound is selected from D-serine, L-serine, D-alanine and L-alanine.  
     
     
         29 . The D-serine transport inhibitor compound according to  claim 27 , wherein the compound is a selective D-serine transport inhibitor.  
     
     
         30 . The D-serine transport inhibitor compound according to  claim 27 , which is selective for glycine uptake inhibition.  
     
     
         31 . The D-serine transport inhibitor compound according to  claim 30 , wherein the inhibitor compound is D-serine dodecylamide.  
     
     
         32 . The D-serine transport inhibitor compound according to  claim 29 , which is selective for D-serine uptake inhibition.  
     
     
         33 . The D-serine transport inhibitor compound according to  claim 32 , wherein the inhibitor compound is D-alanine dodecylamide.  
     
     
         34 . A process for augmentation of N-methyl-D-aspartate receptor-mediated neurotransmission in vivo which comprises administration of an effective amount of a selective D-serine transport inhibitor.  
     
     
         35 . The process of  claim 34 , wherein a psychotic disorder associated with decreased N-methyl-D-aspartate receptor-mediated neurotransmission is treated.  
     
     
         36 . The process of  claim 34 , wherein schizophrenia is treated.  
     
     
         37 . The process of  claim 34 , wherein a neuropsychiatric disorder selected from the group consisting of Alzheimer's disease, bipolar illness, depression and an anxiety disorder is treated.  
     
     
         38 . The process of  claim 34 , wherein the inhibitor compound is a serine or alanine compound having a hydrophobic group linked to either the C-or N-terminus, wherein the hydrophobic group is selected from the group consisting of a C1-13 alkyl group optionally substituted with a halogen atom, a phenyl group optionally substituted with a C1-13 alkyl group, a cyano group and a halogen atom.  
     
     
         39 . The process according to  claim 38 , wherein the serine or alanine compound is selected from D-serine, L-serine, D-alanine and L-alanine.  
     
     
         40 . The process according to  claim 38 , wherein the inhibitor is selective for D-serine uptake inhibition.  
     
     
         41 . The process according to  claim 40 , wherein the inhibitor is D-alanine dodecylamide.  
     
     
         42 . The process according to  claim 38 , wherein the inhibitor is selective for glycine uptake inhibition.  
     
     
         43 . The process according to  claim 42 , wherein the inhibitor is D-serine dodecylamide.  
     
     
         44 . A composition for treating schizophrenia comprising an effective amount of a D-serine transport inhibitor according to  claim 27  and a pharmaceutically acceptable carrier.