Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4-5
|
| pubmed:dateCreated |
1997-9-15
|
| pubmed:abstractText |
SB 242084 has a high affinity (pKi 9.0) for the cloned human 5-HT2C receptor and 100- and 158-fold selectivity over the closely related cloned human 5-HT2B and 5-HT2A subtypes respectively. SB 242084 had over 100-fold selectivity over a range of other 5-HT, dopamine and adrenergic receptors. In studies of 5-HT-stimulated phosphatidylinositol hydrolysis using SH-SY5Y cells stably expressing the cloned human 5-HT2C receptor, SB 242084 acted as an antagonist with a pKb of 9.3, which closely resembled its corresponding receptor binding affinity. SB 242084 potently inhibited m-chlorophenylpiperazine (mCPP, 7 mgkg i.p. 20 min pre-test)-induced hypolocomotion in rats, a model of in vivo central 5-HT2C receptor function, with an ID50 of 0.11 mg/kg i.p., and 2.0 mg/kg p.o. SB 242084 (0.1-1 mg/kg i.p.) exhibited an anxiolytic-like profile in the rat social interaction test, increasing time spent in social interaction, but having no effect on locomotion. SB 242084 (0.1-1 mg/kg i.p.) also markedly increased punished responding in a rat Geller-Seifter conflict test of anxiety, but had no consistent effect on unpunished responding. A large acute dose of SB 242084 (30 mg/kg p.o.) had no effect on seizure susceptibility in the rat maximal electroshock seizure threshold test. Also, while SB 242084 (2 and 6 mg/kg p.o. 1 hr pre-test) antagonized the hypophagic response to mCPP, neither acute nor subchronic administration of the drug, for 5 days at 2 or 6 mg/kg p.o. twice daily, affected food intake or weight gain. The results suggest that SB 242084 is the first reported selective potent and brain penetrant 5-HT2C receptor antagonist and has anxiolytic-like activity, but does not possess either proconvulsant or hyperphagic properties which are characteristic of mutant mice lacking the 5-HT2C receptor.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-(3-chlorophenyl)piperazine,
http://linkedlifedata.com/resource/pubmed/chemical/Aminopyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0028-3908
|
| pubmed:author |
pubmed-author:AvenellK YKY,
pubmed-author:BlackburnT PTP,
pubmed-author:BrightFF,
pubmed-author:BromidgeSS,
pubmed-author:BrownA MAM,
pubmed-author:ForbesI TIT,
pubmed-author:HollandVV,
pubmed-author:KennettG AGA,
pubmed-author:MiddlemissD NDN,
pubmed-author:RileyGG,
pubmed-author:SteadBB,
pubmed-author:TrainLL,
pubmed-author:UptonNN,
pubmed-author:WoodM DMD
|
| pubmed:issnType |
Print
|
| pubmed:volume |
36
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
609-20
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:9225286-Aminopyridines,
pubmed-meshheading:9225286-Animals,
pubmed-meshheading:9225286-Anxiety,
pubmed-meshheading:9225286-Brain,
pubmed-meshheading:9225286-Conflict (Psychology),
pubmed-meshheading:9225286-Electroshock,
pubmed-meshheading:9225286-Feeding Behavior,
pubmed-meshheading:9225286-Humans,
pubmed-meshheading:9225286-Indoles,
pubmed-meshheading:9225286-Male,
pubmed-meshheading:9225286-Motor Activity,
pubmed-meshheading:9225286-Phosphatidylinositols,
pubmed-meshheading:9225286-Piperazines,
pubmed-meshheading:9225286-Rats,
pubmed-meshheading:9225286-Rats, Sprague-Dawley,
pubmed-meshheading:9225286-Receptors, Serotonin,
pubmed-meshheading:9225286-Serotonin Antagonists,
pubmed-meshheading:9225286-Serotonin Receptor Agonists,
pubmed-meshheading:9225286-Social Behavior,
pubmed-meshheading:9225286-Tumor Cells, Cultured
|
| pubmed:articleTitle |
SB 242084, a selective and brain penetrant 5-HT2C receptor antagonist.
|
| pubmed:affiliation |
Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, Harlow, Essex, U.K.
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| pubmed:publicationType |
Journal Article
|