Linked Life Data

9651150

Source:http://linkedlifedata.com/resource/pubmed/id/9651150

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1998-7-24
pubmed:abstractText
The discovery of a series of novel halogenated arylsulfonamides (HAS) as new sigma receptor binding tumor imaging agents is described. Several substituted halogenated sulfonamides have been prepared and characterized. Target compounds were examined for their affinity for sigma1 and sigma2 receptor subtypes using guinea pig brain membranes and rat liver membranes, respectively. A number of substituted halogenated sulfonamides displayed subnanomolar affinities for sigma1 sites and low nanomolar affinities for sigma2 subtype receptors. A limited structure-activity relationship study of this chemical series is discussed. The radioiodination (I-125) of one congener member (4-[125I]iodo-N-[2-(1'-piperidinyl)ethyl]benzenesulfonamide, 4-[125I]IPBS) was accomplished in high yields. The in vitro competition binding studies of 4-[125I]IPBS in guinea pig brain membranes with sigma receptor binding ligands confirmed its sigma pharmacology. The rank order of potency was BD1008 (N-[2-(3, 4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine) > 4-IPBS > haloperidol > (+)-pentazocine > DTG (1, 3-di-o-tolylguanidine) > (-)-pentazocine. The inhibition constants (IC50) were 0.70, 1.46, 6.28, 10.4, 87.2, and 152 nM, respectively, and are consistent with labeling of sigma1 receptors. The tumor imaging potential of 4-[125I]IPBS was studied in C57 black mice bearing B16 melanoma xenograft. A high tumor uptake of 4-[125I]IPBS was observed (7.40% ID/g) at 1 h postinjection. The wash out of activity from the tumor was slow at 6 h postinjection (7.22% ID/g). The tumor also had the highest amount of radioactivity (1.54% ID/g) at 24 h postinjection. These results demonstrate that radiohalogenated benzenesulfonamides could be a potentially useful class of compounds in nuclear oncologic scintigraphy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2445-50
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9651150-Animals, pubmed-meshheading:9651150-Binding, Competitive, pubmed-meshheading:9651150-Brain, pubmed-meshheading:9651150-Guinea Pigs, pubmed-meshheading:9651150-Iodine Radioisotopes, pubmed-meshheading:9651150-Isotope Labeling, pubmed-meshheading:9651150-Ligands, pubmed-meshheading:9651150-Liver, pubmed-meshheading:9651150-Melanoma, pubmed-meshheading:9651150-Membranes, pubmed-meshheading:9651150-Mice, pubmed-meshheading:9651150-Neoplasm Transplantation, pubmed-meshheading:9651150-Neoplasms, pubmed-meshheading:9651150-Piperidines, pubmed-meshheading:9651150-Radiopharmaceuticals, pubmed-meshheading:9651150-Rats, pubmed-meshheading:9651150-Receptors, sigma, pubmed-meshheading:9651150-Structure-Activity Relationship, pubmed-meshheading:9651150-Sulfonamides, pubmed-meshheading:9651150-Tissue Distribution, pubmed-meshheading:9651150-Transplantation, Heterologous, pubmed-meshheading:9651150-Tumor Cells, Cultured
pubmed:year
1998
pubmed:articleTitle
Substituted halogenated arylsulfonamides: a new class of sigma receptor binding tumor imaging agents.
pubmed:affiliation
Radiopharmaceutical Chemistry Section, Department of Radiology, The George Washington University Medical Center, Washington, D.C. 20037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.