Original articleGlycine transporter I inhibitor, N-Methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia
Section snippets
Subjects
Patients were recruited from the day program and inpatient units of Taipei City Psychiatry Center and Kaoshiung Medical University, which are major medical centers in Taiwan. The research protocol was approved by the above Institutional Review Boards (IRBs). Sarcosine is a natural amino acid. It is regulated as food supplement and investigational new drug application (IND) is not required in Taiwan. After a description of the study to the patients, written informed consent was obtained.
Results
Characteristics of the schizophrenic illness were similar in the two groups, except the onset of the illness (Table 1). Both groups had similar ratios of paranoid versus nonparanoid subtypes of schizophrenia. Though the sarcosine group has earlier onset of the illness than the placebo group, the sarcosine group improved in the outcome measures, but the placebo group did not improve.
Discussion
Our findings indicate that sarcosine, acting as an antagonist on the GlyT-1, can improve positive, negative, cognitive, and other psychiatric symptoms of schizophrenia. Since there is no other neurotransmission site at which sarcosine acts except the known GlyT-1 site, the effect of sarcosine is likely due to its action on the GlyT-1. Together with the positive findings of D-serine (Tsai et al 1998a), glycine (Heresco-Levy et al 1999), and D-cycloserine treatments van Berckel et al., 1996, Goff
Acknowledgements
We thank Dr. Joseph T. Coyle for his critical review of the manuscript. Sarcosine is protected by US patent 6228875, for which GT is an inventor. This work was supported by funding from the National Science Council (Taiwan) NSC 91-2314-B-039-033 and the National Health Research Institutes (Taiwan) NHRI-EX-91-9134PI and NHRI-EX-92-9134PI (HL). GT is supported partly by Grant Nos. P50 MH60450-01 and R01 MH51290-08, a Stanley Foundation Research Award, and a National Alliance for Research on
References (41)
- et al.
Direct calcium binding results in activation of brain serine racemase
J Biol Chem
(2002) - et al.
Cloning and mapping of the cDNA for human sarcosine dehydrogenase, a flavoenzyme defective in patients with sarcosinemia
Genomics
(1999) - et al.
A.E. Bennett Research Award. Reversal of phencyclidine-induced effects by glycine and glycine transport inhibitors
Biol Psychiatry
(1999) - et al.
The NMDA receptor antagonist CPP abolishes neurogenic ‘wind up pain’ after intrathecal administration in humans
Pain
(1992) - et al.
Physiological and pathophysiological roles of excitatory amino acids during central nervous system development
Brain Res Rev
(1990) - et al.
Cloning and expression of a glycine transporter reveal colocalization with NMDA receptors
Neuron
(1992) - et al.
Glutamatergic neurotransmission involves structural and clinical deficits of schizophrenia
Biol Psychiatry
(1998) - et al.
D-serine added to antipsychotic for the treatment of schizophrenia
Biol Psychiatry
(1998) - et al.
Efficacy and tolerance of D-cycloserine in drug-free schizophrenic patients
Biol Psychiatry
(1996) - American Psychiatric Association (1994a): Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington,...