PMID- 23427107
OWN - NLM
STAT- MEDLINE
DCOM- 20131127
LR  - 20130409
IS  - 1531-8257 (Electronic)
IS  - 0885-3185 (Linking)
VI  - 28
IP  - 4
DP  - 2013 Apr
TI  - Glycine site agonists of the N-methyl-D-aspartate receptor and Parkinson's 
      disease: a hypothesis.
PG  - 419-24
LID - 10.1002/mds.25306 [doi]
AB  - Limitations of current pharmacological approaches to Parkinson's disease (PD) 
      highlight the need for the development of nondopaminergic therapeutic strategies. 
      The potential role of glutamatergic neurotransmission modulators, including those 
      active at the N-methyl-D-aspartate receptor (NMDAR), is presently under 
      investigation. Most literature proposes the use of NMDAR antagonists based on 
      neurodegenerative theories of NMDAR function. Nevertheless, NMDAR antagonism has 
      proven disappointing in clinical trials and may be associated with serious 
      adverse events. More recent theories indicate that NMDAR target selectivity may 
      be a cardinal prerequisite for efficacy, with present efforts being devoted 
      primarily to development of NMDAR-NR2B subunit antagonists. We propose a novel 
      hypothesis according to which NMDAR stimulation, accomplished through allosteric 
      modulation via the glycine modulatory site, may be beneficial in late-phase PD. 
      This hypothesis stems from: (1) meta-analysis of randomized controlled trials 
      performed in schizophrenia, indicating that glycine site agonists (eg, glycine, 
      D-serine) alleviate antipsychotic-induced parkinsonian symptoms; (2) clinical 
      observations indicating that NMDAR hypofunction is associated with motor 
      disturbances; (3) results of a preliminary D-serine trial in PD; (4) data 
      indicating glycine efficacy in a rat tardive dyskinesia model; and (5) no 
      evidence of excitotoxic damage following chronic high-dose glycine nutritional 
      supplementation. This hypothesis is discussed in the context of glycine site 
      agonist effects on intrasynaptic NMDAR subunits and striatal synaptic plasticity.
CI  - Copyright (c) 2013 Movement Disorders Society.
FAU - Heresco-Levy, Uriel
AU  - Heresco-Levy U
AD  - Psychiatry Department, Ezrath Nashim-Herzog Memorial Hospital and Hebrew 
      University Hadassah Medical School, Jerusalem, Israel. heresco@md.huji.ac.il
FAU - Shoham, Shai
AU  - Shoham S
FAU - Javitt, Daniel C
AU  - Javitt DC
LA  - eng
PT  - Editorial
PT  - Review
DEP - 20130220
PL  - United States
TA  - Mov Disord
JT  - Movement disorders : official journal of the Movement Disorder Society
JID - 8610688
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - *Clinical Trials as Topic
MH  - Disease Models, Animal
MH  - Glycine/*antagonists & inhibitors
MH  - Humans
MH  - Parkinson Disease/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*agonists/metabolism
MH  - Schizophrenia/metabolism
EDAT- 2013/02/22 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/02/22 06:00
PHST- 2012/05/10 00:00 [received]
PHST- 2012/10/26 00:00 [revised]
PHST- 2012/11/05 00:00 [accepted]
PHST- 2013/02/22 06:00 [entrez]
PHST- 2013/02/22 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - 10.1002/mds.25306 [doi]
PST - ppublish
SO  - Mov Disord. 2013 Apr;28(4):419-24. doi: 10.1002/mds.25306. Epub 2013 Feb 20.