title: D-alanine added to antipsychotics for the treatment of schizophrenia.
abstract: BACKGROUND
  Hypofunction of the N-methyl-d-aspartate (NMDA) subtype glutamate receptor had been implicated in the pathophysiology of schizophrenia. Treatment with D-serine, glycine, endogenous full agonists of the glycine site of the NMDA receptor (NMDA-glycine site), D-cycloserine, a partial agonist, or sarcosine, a glycine transporter-1 inhibitor, improves the symptoms of schizophrenia. D-alanine is another endogenous agonist of the NMDA-glycine site that might have beneficial effects on schizophrenia.
  
  
  METHODS
  Thirty-two schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-alanine (100 mg/kg/day), which was added to their stable antipsychotic regimens. Measures of clinical efficacy and side effects were determined every other week.
  
  
  RESULTS
  Patint who received D-alanine treatment revealed significant reductions in their Clinical Global Impression Scale and Positive and Negative Syndrome Scale (PANSS) total scores. The Scale for the Assessment of Negative Symptoms and PANSS subscores of positive and cognitive symptoms were improved. D-alanine was well tolerated, and no significant side effect was noted.
  
  
  CONCLUSIONS
  The significant improvement with the D-alanine further supports the hypothesis of hypofunction of NMDA neurotransmission in schizophrenia and strengthens the proof of the principle that NMDA-enhancing treatment is a promising approach for the pharmacotherapy of schizophrenia.
authors.affiliation: Department of Psychiatry, Harbor-UCLA Medical Center, Torrance, California 90509, USA. etsai@labiomed.org
authors.forename: Guochuan E
authors.initials: GE
authors.lastname: Tsai
authors.forename: Pinchen
authors.initials: P
authors.lastname: Yang
authors.forename: Yue-Cune
authors.initials: YC
authors.lastname: Chang
authors.forename: Mian-Yoon
authors.initials: MY
authors.lastname: Chong
mesh_terms: D000328:Adult; D000409:Alanine / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D018009:Receptors, Glycine / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D000409:Alanine