Document Detail

The effects of the glycine reuptake inhibitor R213129 on the central nervous system and on scopolamine-induced impairments in psychomotor and cognitive function in healthy subjects.
MedLine Citation:
PMID:  20142308     Owner:  NLM     Status:  In-Process    
In this study the effects of R213129, a selective glycine transporter 1 inhibitor, on central nervous system function were investigated in healthy males in the absence and presence of scopolamine. This was a double-blind, placebo-controlled, 4-period crossover ascending dose study evaluating the following endpoints: body sway, saccadic and smooth pursuit eye movements, pupillometry, electroencephalography, visual analogue scales for alertness, mood, calmness and psychedelic effects, adaptive tracking, finger tapping, Visual and Verbal Learning Task, Stroop test, hormone levels and pharmacokinetics. R213129 dose levels were selected based on exposure levels that blocked the GlyT1 sites >50% in preclinical experiments. Forty-three of the 45 included subjects completed the study. Scopolamine significantly affected almost every central nervous system parameter measured in this study. R213129 alone compared with placebo did not elicit pharmacodynamic changes. R213129 had some small effects on scopolamine-induced central nervous system impairments. Scopolamine-induced finger tapping impairment was further enhanced by 3 mg R213129 with 2.0 taps/10 seconds (95% CI -4.0, -0.1), electroencephalography alpha power was increased by 10 mg R213129 with respectively 12.9% (0.7, 26.6%), scopolamine-induced impairment of the Stroop test was partly reversed by 10 mg R213129 with 59 milliseconds (-110, -7). Scopolamine produced robust and consistent effects in psychomotor and cognitive function in healthy volunteers. The most logical reason for the lack of R213129 effects seems to be that the central nervous system concentrations were too low. The effects of higher doses in healthy volunteers and the clinical efficacy in patients remain to be established.
M Liem-Moolenaar; R W M Zoethout; P de Boer; M Schmidt; M L de Kam; A F Cohen; K L Franson; J M A van Gerven
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Publication Detail:
Type:  Journal Article     Date:  2010-02-08
Journal Detail:
Title:  Journal of psychopharmacology (Oxford, England)     Volume:  24     ISSN:  1461-7285     ISO Abbreviation:  J. Psychopharmacol. (Oxford)     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8907828     Medline TA:  J Psychopharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1671-9     Citation Subset:  IM    
Centre for Human Drug Research, Leiden, The Netherlands.
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