lycine Transporter I Inhibitor , N - methylglycine Sarcosine ) , Added to Clozapine for the reatment of Schizophrenia

ackground: Agonists at the N-methyl-D-aspartate (NMDA)-glycine site (D-serine, glycine, D-alanine and D-cycloserine) and glycine ransporter-1 (GlyT-1) inhibitor (N-methylglycine, or called sarcosine) both improve the symptoms of stable chronic schizophrenia atients receiving concurrent antipsychotics. Previous studies, however, found no advantage of D-serine, glycine, or D-cycloserine dded to clozapine. The present study aims to determine the effects of sarcosine adjuvant therapy for schizophrenic patients receiving lozapine treatment. ethods: Twenty schizophrenic inpatients enrolled in a 6-week double-blind, placebo-controlled trial of sarcosine (2 g/day) which as added to their stable doses of clozapine. Measures of clinical efficacy and side-effects were determined every other week. esults: Sarcosine produced no greater improvement when co-administered with clozapine than placebo plus clozapine at weeks 2, , and 6. Sarcosine was well tolerated and no significant side-effect was noted. onclusions: Unlike patients treated with other antipsychotics, patients who received clozapine treatment exhibit no improvement by dding sarcosine or agonists at the NMDA-glycine site. Clozapine possesses particular efficacy, possibly related to potentiation of MDA-mediated neurotransmission. This may contribute to the clozapine’s unique clinical efficacy and refractoriness to the addition f NMDA-enhancing agents.