Identification of an orally bioavailable, potent, and selective inhibitor of GlyT1

ACS Medicinal Chemistry Letters

Volumn 1, Issue 7, 2010, Pages 350-354

  Blackaby, Wesley P ^a,c   Lewis, Richard T ^a   Thomson, Joanne L ^a   Jennings, Andrew S R ^a   Goodacre, Simon C ^a   Street, Leslie J ^a   MacLeod, Angus M ^a   Pike, Andrew ^a   Wood, Suzanne ^a   Thomas, Steve ^a   Brown, Terry A ^a   Smith, Alison ^a   Pillai, Gopalan ^a   Almond, Sarah ^a   Guscott, Martin R ^a   Burns, H Donald ^b   Eng, Waisi ^b   Ryan, Christine ^b   Cook, Jacquelynn ^b   Hamill, Terence G ^b  

^a NEUROSCIENCE RESEARCH CENTRE   (United Kingdom)

^b MERCK RESEARCH LABORATORIES   (United States)

^c Bio Focus ^*  (United Kingdom)

Author keywords

DCCCyB; GlyT1; Inhibitor; PET tracer ligand; structure activity relationship

Indexed keywords

GLYCINE TRANSPORTER 1; GLYCINE TRANSPORTER 1 INHIBITOR; NEUROLEPTIC AGENT; TRACER; UNCLASSIFIED DRUG;

ARTICLE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CLEARANCE; DRUG STRUCTURE; HUMAN; IC 50; IN VIVO STUDY; LIVER MICROSOME; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RHESUS MONKEY; SCHIZOPHRENIA; STRUCTURE ACTIVITY RELATION;

MACACA MULATTA;

EID: 77958086613     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml1001085     Document Type: Article

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26. 11C]CMPyPB, Glycine Transporter 1 (GlyT1) PET Radiotracers Synapse, in press.
27. 2O:PEG400) as an iv bolus plus infusion. The tracer was administered 1 h after the start of the infusion. PET Regions of Interest: For each scan, a static (or summed) PET image was obtained by summing the dynamic frames acquired during the acquisition. Regions of interest (ROIs) were drawn on the summed images in the striatum (caudate and putamen), thalamus, cortical regions (mainly occipital cortex), and white matter. Then, ROIs were projected into the dynamic scans to obtain the corresponding time-activity curves (TACs). TACs were expressed in standard uptake value (SUV) units using the monkey body weight and the tracer injected dose as: TAC (SUV) = 1000 Ã - TAC (Bq) Ã - weight (kg) / injected tracer dose (Bq)