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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1998-12-18
|
| pubmed:abstractText |
1. Human 5-HT1B (h5-HT1B) and human 5-HT1D (h5-HT1D) receptors show remarkably similar pharmacology with few compounds discriminating the receptors. We report here on a novel compound, SB-224289 (1'-Methyl-5-[[2'-methyl-4'-(5-methyl- 1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro spiro [furo [2,3-f]indole-3,4'-piperidine] oxalate), which has high affinity for h5-HT1B receptors (pK1=8.16+/-0.06) and displays over 75 fold selectivity for the h5-HT1B receptor over all other 5-HT receptors including the h5-HT1D receptor and all other receptors tested thus far. 2. Functional activity of SB-224289 was measured in a [15S]GTPgammaS binding assay on recombinant h5-HT1B and h5-HT1D receptors expressed in Chinese Hamster Ovary (CHO) cells. SB-224289 displayed negative intrinsic activity at both receptors with higher potency at h5-HT1B receptors. SB-224289 caused a rightward shift of agonist concentration response curves consistent with competitive antagonism and generated affinities comparable with those obtained from competition radioligand receptor binding studies. 3. SB-224289 potentiated [3H]5-HT release from electrically stimulated guinea-pig cerebral cortical slices to the same extent as as the non-selective 5-HT1 antagonist methiothepin. SB-224289 also fully reversed the inhibitory effect of exogenously superfused 5-HT on electrically stimulated release. 4. Using SB-224289 as a tool compound, we confirm that in guinea-pig cerebral cortex the terminal 5-HT autoreceptor is of the 5-HT1B subtype.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/HTR1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidones,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT1B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SB 22489G,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Spiro Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfur Radioisotopes
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0007-1188
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
125
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
202-8
|
| pubmed:dateRevised |
2008-11-20
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| pubmed:meshHeading |
pubmed-meshheading:9776361-Animals,
pubmed-meshheading:9776361-CHO Cells,
pubmed-meshheading:9776361-Cricetinae,
pubmed-meshheading:9776361-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:9776361-HeLa Cells,
pubmed-meshheading:9776361-Humans,
pubmed-meshheading:9776361-Piperidones,
pubmed-meshheading:9776361-Radioligand Assay,
pubmed-meshheading:9776361-Receptor, Serotonin, 5-HT1B,
pubmed-meshheading:9776361-Receptors, Serotonin,
pubmed-meshheading:9776361-Recombinant Proteins,
pubmed-meshheading:9776361-Serotonin,
pubmed-meshheading:9776361-Serotonin Antagonists,
pubmed-meshheading:9776361-Spiro Compounds,
pubmed-meshheading:9776361-Sulfur Radioisotopes
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
SB-224289--a novel selective (human) 5-HT1B receptor antagonist with negative intrinsic activity.
|
| pubmed:affiliation |
Department of Neurosciences, SmithKline Beecham Pharmaceuticals, Harlow, Essex.
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| pubmed:publicationType |
Journal Article
|