Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia.
BACKGROUND
Hypofunction of N-methyl-D-aspartate glutamate receptor had been implicated in the pathophysiology of schizophrenia. Treatment with D-serine or glycine, endogenous full agonists of the glycine site of N-methyl-D-aspartate receptor, or D-cycloserine, a partial agonist, improve the symptoms of schizophrenia. N-methylglycine (sarcosine) is an endogenous antagonist of glycine transporter-1, which potentiates glycine's action on N-methyl-D-aspartate glycine site and can have beneficial effects on schizophrenia.


METHODS
Thirty-eight schizophrenic patients were enrolled in a 6-week double-blind, placebo-controlled trial of sarcosine (2 g/d), which was added to their stable antipsychotic regimens. Twenty of them received risperidone. Measures of clinical efficacy and side effects were determined every other week.


RESULTS
Patient who received sarcosine treatment revealed significant improvements in their positive, negative, cognitive, and general psychiatric symptoms. Similar therapeutic effects were observed when only risperidone-treated patients were analyzed. Sarcosine was well-tolerated, and no significant side effect was noted.


CONCLUSIONS
Sarcosine treatment can benefit schizophrenic patients treated by antipsychotics including risperidone. The significant improvement with the sarcosine further supports the hypothesis of N-methyl-D-aspartate receptor hypofunction in schizophrenia. Glycine transporter-1 is a novel target for the pharmacotherapy to enhance N-methyl-D-aspartate function.
Tsai
Guochuan
G
Laboratory of Molecular and Psychiatric Neuroscience (GT), McLean Hospital and Harvard Medical School, Boston, Massachusetts 02478, USA.
Lane
Hsien-Yuan
HY
Yang
Pinchen
P
Chong
Mian-Yoon
MY
Lange
Nicholas
N
D000328:Adult; D000342:Affective Symptoms / Q000209:etiology / Q000517:prevention & control*; D026921:Amino Acid Transport Systems, Neutral / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D050487:Glycine Plasma Membrane Transport Proteins; D006801:Humans; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D018967:Risperidone / Q000008:administration & dosage*; D012521:Sarcosine / Q000008:administration & dosage*; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*
D026921:Amino Acid Transport Systems, Neutral; D014150:Antipsychotic Agents; D050487:Glycine Plasma Membrane Transport Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C493268:SLC6A9 protein, human; D018967:Risperidone; D012521:Sarcosine