Document Detail

Synthesis and characterization of [³H]-SN56, a novel radioligand for the σ₁ receptor.
MedLine Citation:
PMID:  21130085     Owner:  NLM     Status:  MEDLINE    
The study of the binding characteristics of σ ligands in vivo and in vitro requires radiolabeled probes with high affinity and selectivity. The radioligand presently used for in vitro studies of the σ₁ receptor, [³H](+)-pentazocine, has significant limitations; it is difficult to synthesize, has limited chemical stability, and can be problematic to obtain. Evaluation of a series of novel 2(3H)-benzothiazolone compounds revealed SN56 to have sub-nanomolar and preferential affinity for the σ₁ subtype, relative to σ₂ and non-sigma, binding sites. The goal of this study was to characterize the binding of [³H]-SN56 to σ₁ receptors isolated from rat brain. Standard in vitro binding techniques were utilized to 1) determine the specificity and affinity of binding to σ₁ receptors, 2) confirm that[³H]-SN56 labels sites previously identified as σ₁ by comparing binding to sites labeled by [³H](+)-pentazocine, and 3) characterize the kinetics of binding. The results indicate that [³H]-SN56 exhibits 1) specific, saturable, and reversible binding to the σ₁ receptor, with B(max)=340±10 fmol/mg and K(d)=0.069±0.0074 nM, 2) competitive displacement by classical sigma compounds, yielding σ₁ K(i) values consistent with those reported in the literature, and 3) binding kinetics compatible with a 90 min incubation, and filtration for separation of free and bound radioligand. The results of these studies suggest that [(3)H]-SN56 may serve as a viable alternative to [³H](+)-pentazocine in radioligand binding assays.
James A Fishback; Christophe Mesangeau; Jacques H Poupaert; Christopher R McCurdy; Rae R Matsumoto
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-12-02
Journal Detail:
Title:  European journal of pharmacology     Volume:  653     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-14     Completed Date:  2011-05-02     Revised Date:  2013-07-31    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506, USA.
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MeSH Terms
Azepines / chemical synthesis,  metabolism*
Benzothiazoles / chemical synthesis,  metabolism*
Binding Sites
Brain / metabolism
Pentazocine / metabolism
Protein Binding
Radioligand Assay / methods*
Radiopharmaceuticals / metabolism*
Rats, Sprague-Dawley
Receptors, sigma / metabolism*
Grant Support
Reg. No./Substance:
0/3-(2-(azepan-1-yl)ethyl)-6-propylbenzo(d)thiazol-2(3H)-one; 0/Azepines; 0/Benzothiazoles; 0/Radiopharmaceuticals; 0/Receptors, sigma; 0/sigma-1 receptor; 359-83-1/Pentazocine

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