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Clin Neuropharmacol. 1991 Jun;14(3):268-72.

An NMDA intervention strategy in schizophrenia with "low-dose" milacemide.

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Department of Veteran Affairs Medical Center, Washington, D.C. 20422.


Drugs (e.g., PCP) which interfere with glutamatergic transmission at the N-methyl D-aspartate (NMDA) subclass of glutamate receptors precipitate both positive and negative symptoms of psychosis in humans. Based on a proposed "glutamatergic deficiency" in schizophrenia, pharmacologic facilitation of NMDA-mediated neural transmission by direct stimulation of the strychine-insensitive glycine binding site was attempted with "low-dose" milacemide, an acylated "prodrug" of glycine that readily crosses the blood brain barrier and is converted into glycine in the brain. In a prior study, "high-dose" milacemide proved to have no therapeutic utility in schizophrenia. The failure was thought, possibly, to be related to higher doses of milacemide having antagonist actions at the NMDA receptor complex. In the current study, "low-dose" milacemide (400 mg/day), as the sole pharmacotherapeutic agent, was also without significant clinical benefit. Despite our negative findings for milacemide, other strategies for facilitating NMDA-mediated neural transmission in schizophrenia might be worth pursuing.

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