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

Abstract:

: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.

journal_name

Clin Neuropharmacol

authors

Rosse RB,Schwartz BL,Davis RE,Deutsch SI

doi

10.1097/00002826-199106000-00012

subject

Has Abstract

pub_date

1991-06-01 00:00:00

pages

268-72

issue

3

eissn

0362-5664

issn

1537-162X

journal_volume

14

pub_type

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