GLYCINERGIC AUGMENTATION OF NMDA RECEPTOR-MEDIATED NEUROTRANSMISSION IN THE TREATMENT OF SCHIZOPHRENIA

Phencyclidine (Pop) induces a psychotic state closely resembling schiz ophrenia in normal individuals, Pop and related agents induce their un ique behavioral effects by blocking neurotransmission mediated at N-me thyl-D-aspartate (NMDA)-type glutamate receptors, indicating that dysf unction of NMDA receptor-mediated neurotransmission may play a crucial role in the pathophysiology of schizophrenia. NMDA receptors are acti vated by the amino acids glutamate and glycine, working at independent binding sites, Glutamate cannot be administered exogenously because o f excitotoxicity, In contrast, glycine administered exogenously may po tentiate NMDA receptor-mediated neurotransmission in vivo following pe ripheral administration, In rodents, glycine is effective in elevating brain glycine levels and reversing pop-induced hyperactivity at doses of 0.8 g/kg and above, Three studies have now been completed utilizin g moderate to high (0.4-0.8 g/kg/day) doses of glycine, added to neuro leptics, for the treatment of schizophrenia, Across studies, 15 to 30 percent improvement in negative symptoms was observed with no correspo nding worsening of positive symptoms. Although preliminary, these stud ies indicate that dietary supplementation with glycine or treatment wi th other glycinergic agents may be effective in the treatment of schiz ophrenia.