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.

What is claimed:  
     
         1 . A method for treatment of neuropsychiatric disorders which comprises administration of a D-serine transport inhibitor at a dose sufficient to enhance NMDA receptor-mediated neurotransmission in vivo.  
     
     
         2 . The method of  claim 1  wherein the disorder is associated with decreased N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission.  
     
     
         3 . The method of  claim 1  wherein the disorder is a psychotic disorder.  
     
     
         4 . The method of  claim 3  wherein the psychotic disorder is schizophrenia  
     
     
         5 . The method of  claim 1  wherein the disorder is Alzheimer's disease, bipolar illness, depression and anxiety disorders, stroke or epilepsy.  
     
     
         6 . The method of  claim 1  wherein the disorder is age associated memory impairment, closed head injury or attention deficit disorder.  
     
     
         7 . The method of  claim 1  wherein such agent is administered orally.  
     
     
         8 . The method of  claim 1  wherein a D-serine transport inhibitor is administered parenterally.  
     
     
         9 . A method for augmentation of N-methyl-D-aspartate receptor-mediated neurotransmission in vivo which comprises administration of a D-serine transport antagonist.  
     
     
         10 . The method of  claim 1  or  9  wherein the antagonist is an inhibitor of D-serine transport mediated through system ASC.  
     
     
         11 . The method of  claim 1  or  9  wherein the antagonist is an inhibitor of systems L, N, A or Gly.  
     
     
         12 . The method of  claim 1  or  9  wherein the antagonist is an inhibitor of alanine-sensitive D-serine transport.  
     
     
         13 . The method of  claim 1  or  9  where the antagonist is an inhibitor of alanine-insensitive D-serine transport.  
     
     
         14 . The method of  claim 1  or  9  wherein the agent is glycyldodecylamide, D-serine dodecylamide or D-alanine dodecylamide.  
     
     
         15 . The method of  claim 1  or  9  wherein the agent is used in combination with typical or atypical antipsychotics administered orally, parenterally or by depot formulation.  
     
     
         16 . The method of  claim 1  or  9  wherein the agent is used in combination with other treatments commonly used in schizophrenia, including but not limited to antidepressants, mood stabilizers, or antianxiety agents.  
     
     
         17 . The method of  claim 1  or  9  wherein the agent is used in combination with a glycine transport inhibitor.  
     
     
         18 . A composition for treating schizophrenia incorporating a D-serine transport inhibitor.  
     
     
         19 . A composition of  claim 18 , wherein the inhibitor is glycyldodecylamide, D-serine dodecylamide or D-alanine dodecylamide.  
     
     
         20 . A composition of  claim 18  wherein the inhibitor is a derivative of serine or alanine having effectiveness in inhibiting D-serine transport in vivo.  
     
     
         21 . A composition of  claim 18  wherein the D-serine transport inhibitor is combined with a typical or atypical antipsychotic agent administerable orally or parenterally.  
     
     
         22 . A composition of  claim 20  wherein the derivative is a hydrophobic derivative of serine or alanine.  
     
     
         23 . A composition of  claim 22  wherein the derivative is serine or alanine having a hydrophobic group linked to at least one of the C- and N-terminus.  
     
     
         24 . A composition where the hydrophobic group is selected from the group consisting of alkyl (C1-C13), unsubstituted or substituted phenyl, phenylalkyl (C1-C13), cyano, halogen and or haloalkyl (C1-C13)..  
     
     
         25 . A method of  claim 1  wherein a composition of  claim 20  is used.  
     
     
         26 . A method of  claim 9  wherein a composition of  claim 20  is used.