PMID- 25554623
OWN - NLM
STAT- MEDLINE
DCOM- 20150814
LR  - 20160108
IS  - 1879-1379 (Electronic)
IS  - 0022-3956 (Linking)
VI  - 61
DP  - 2015 Feb
TI  - Behavioral and cognitive effects of the N-methyl-D-aspartate receptor co-agonist 
      D-serine in healthy humans: initial findings.
PG  - 188-95
LID - S0022-3956(14)00348-3 [pii]
LID - 10.1016/j.jpsychires.2014.12.007 [doi]
AB  - The efficacy of compounds having agonistic activity at the glycine site 
      associated with the N-methyl-D-aspartate receptor (NMDAR) is presently assessed 
      in psychiatric disorders. In contrast to NMDAR antagonists, the neuropsychiatric 
      effects of NMDAR agonists in the healthy human organism are not known. We studied 
      neuropsychiatric and neurochemical effects of the NMDAR-glycine site obligatory 
      co-agonist d-serine (DSR) in healthy subjects using a randomized, controlled 
      crossover challenge design including a baseline assessment day and two 
      DSR/placebo administration days. Thirty-five subjects aged 23-29 years 
      participated in the study and received a 2.1 g orally administered DSR dose. The 
      main outcome measures were the changes in scores of mood-related Visual Analogue 
      Scale (VAS), Continuous Performance Test-Identical Pairs (CPT-IP), and Rey 
      Auditory Verbal Learning Test (RAVLT). DSR acute administration: (1) was well 
      tolerated and resulted at 2 h in >/= 200 times increase in DSR serum levels; (2) 
      elicited reduced VAS-measured depression and anxiety feelings; (3) improved 
      attention and vigilance as measured by CPT-IP D-prime score; (4) preferentially 
      improved performance in RAVLT list 7 reflecting ability to retain information 
      over interference; (5) had significant but nonspecific effects on Category 
      Fluency and Benton Visual Retention tests; and (6) did not affect glycine and 
      glutamate serum levels. These data indicate that in healthy subjects, DSR reduces 
      subjective feelings of sadness and anxiety and has procognitive effects that are 
      overall opposed to the known effects of NMDAR antagonists. The findings are 
      relevant to translational research of NMDAR function and the development of 
      NMDAR-glycine site treatments for specific psychiatric entities. 
      ClinicalTrials.gov: Behavioral and Cognitive Effects of the N-methyl-D-aspartate 
      Receptor (NMDAR) Co-agonist D-serine in Healthy Humans; 
      http://www.clinicaltrials.gov/ct2/show/NCT02051426?term=NCT02051426&rank=1; 
      NCT02051426.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Levin, Raz
AU  - Levin R
AD  - Research and Psychiatry Departments, Ezrath Nashim-Herzog Memorial Hospital, 
      Jerusalem, Israel.
FAU - Dor-Abarbanel, Adi Ein
AU  - Dor-Abarbanel AE
AD  - Hadassah Medical School, Hebrew University, Jerusalem, Israel.
FAU - Edelman, Shany
AU  - Edelman S
AD  - Hadassah Medical School, Hebrew University, Jerusalem, Israel.
FAU - Durrant, Andrea R
AU  - Durrant AR
AD  - Research and Psychiatry Departments, Ezrath Nashim-Herzog Memorial Hospital, 
      Jerusalem, Israel.
FAU - Hashimoto, Kenji
AU  - Hashimoto K
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba, Japan.
FAU - Javitt, Daniel C
AU  - Javitt DC
AD  - Nathan S. Kline Institute for Psychiatric Research and Columbia University, NY, 
      USA.
FAU - Heresco-Levy, Uriel
AU  - Heresco-Levy U
AD  - Research and Psychiatry Departments, Ezrath Nashim-Herzog Memorial Hospital, 
      Jerusalem, Israel; Hadassah Medical School, Hebrew University, Jerusalem, Israel. 
      Electronic address: urielh@ekmd.huji.ac.il.
LA  - eng
SI  - ClinicalTrials.gov/NCT02051426
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20141224
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 452VLY9402 (Serine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Adult
MH  - Affect/*drug effects
MH  - Anxiety/*drug therapy/psychology
MH  - Cognition/*drug effects
MH  - Cross-Over Studies
MH  - Female
MH  - Glutamic Acid/blood
MH  - Glycine/blood
MH  - Humans
MH  - Male
MH  - Neuropsychological Tests
MH  - Receptors, N-Methyl-D-Aspartate/*agonists
MH  - Serine/administration & dosage/*pharmacology
MH  - Treatment Outcome
MH  - Verbal Learning/drug effects
MH  - Young Adult
OTO - NOTNLM
OT  - Behavior
OT  - Cognition
OT  - N-methyl-d-aspartate receptor
OT  - d-serine
EDAT- 2015/01/03 06:00
MHDA- 2015/08/15 06:00
CRDT- 2015/01/03 06:00
PHST- 2014/09/04 00:00 [received]
PHST- 2014/11/30 00:00 [revised]
PHST- 2014/12/12 00:00 [accepted]
PHST- 2015/01/03 06:00 [entrez]
PHST- 2015/01/03 06:00 [pubmed]
PHST- 2015/08/15 06:00 [medline]
AID - S0022-3956(14)00348-3 [pii]
AID - 10.1016/j.jpsychires.2014.12.007 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2015 Feb;61:188-95. doi: 10.1016/j.jpsychires.2014.12.007. Epub 
      2014 Dec 24.