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rdf:type |
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lifeskim:mentions |
umls-concept:C0002771,
umls-concept:C0020792,
umls-concept:C0034830,
umls-concept:C0038477,
umls-concept:C0205177,
umls-concept:C0205265,
umls-concept:C0205531,
umls-concept:C0226896,
umls-concept:C0442027,
umls-concept:C0521390,
umls-concept:C0669398,
umls-concept:C0669399,
umls-concept:C0682002,
umls-concept:C1527415,
umls-concept:C1555582
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pubmed:issue |
4
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pubmed:dateCreated |
1998-3-17
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pubmed:abstractText |
New members of a previously reported series of 3-pyridyl ether compounds are disclosed as novel, potent analgesic agents acting through neuronal nicotinic acetylcholine receptors. Both (R)-2-chloro-5-(2-azetidinylmethoxy)pyridine (ABT-594, 5) and its S-enantiomer (4) show potent analgesic activity in the mouse hot-plate assay following either intraperitoneal (i.p.) or oral (p.o.) administration, as well as activity in the mouse abdominal constriction (writhing) assay, a model of persistent pain. Compared to the S-enantiomer and to the prototypical potent nicotinic analgesic agent (+/-)-epibatidine, 5 shows diminished activity in models of peripheral side effects. Structure-activity studies of analogues related to 4 and 5 suggest that the N-unsubstituted azetidine moiety and the 2-chloro substituent on the pyridine ring are important contributors to potent analgesic activity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:AndersonD JDJ,
pubmed-author:ArnericS PSP,
pubmed-author:BannonA WAW,
pubmed-author:BriggsC ACA,
pubmed-author:BuckleyM JMJ,
pubmed-author:CampbellJ EJE,
pubmed-author:DeckerM WMW,
pubmed-author:Donnelly-RobertsD LDL,
pubmed-author:HUII,
pubmed-author:HolladayM WMW,
pubmed-author:KuntzweilerT ATA,
pubmed-author:LinN HNH,
pubmed-author:PaiK NKN,
pubmed-author:Piattoni-KaplanMM,
pubmed-author:RytherK BKB,
pubmed-author:WasicakJ TJT,
pubmed-author:WilliamsMM
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
407-12
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:9484491-Administration, Oral,
pubmed-meshheading:9484491-Analgesics, Non-Narcotic,
pubmed-meshheading:9484491-Animals,
pubmed-meshheading:9484491-Azetidines,
pubmed-meshheading:9484491-Diastole,
pubmed-meshheading:9484491-Female,
pubmed-meshheading:9484491-Humans,
pubmed-meshheading:9484491-Injections, Intraperitoneal,
pubmed-meshheading:9484491-Kinetics,
pubmed-meshheading:9484491-Mice,
pubmed-meshheading:9484491-Molecular Structure,
pubmed-meshheading:9484491-Muscle Contraction,
pubmed-meshheading:9484491-Neuroblastoma,
pubmed-meshheading:9484491-Neurons,
pubmed-meshheading:9484491-Nicotinic Agonists,
pubmed-meshheading:9484491-Oocytes,
pubmed-meshheading:9484491-Pain,
pubmed-meshheading:9484491-Pain Measurement,
pubmed-meshheading:9484491-Pyridines,
pubmed-meshheading:9484491-Rats,
pubmed-meshheading:9484491-Receptors, Nicotinic,
pubmed-meshheading:9484491-Recombinant Proteins,
pubmed-meshheading:9484491-Stereoisomerism,
pubmed-meshheading:9484491-Structure-Activity Relationship,
pubmed-meshheading:9484491-Tumor Cells, Cultured,
pubmed-meshheading:9484491-Xenopus
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pubmed:year |
1998
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pubmed:articleTitle |
Identification and initial structure-activity relationships of (R)-5-(2-azetidinylmethoxy)-2-chloropyridine (ABT-594), a potent, orally active, non-opiate analgesic agent acting via neuronal nicotinic acetylcholine receptors.
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pubmed:affiliation |
Neurological and Urological Diseases Research D-47W, Abbott Laboratory, Abbott Park, Illinois 60064-3500, USA. mark.w.holladay@abbott.com
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pubmed:publicationType |
Journal Article
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