Linked Life Data

8410979

Source:http://linkedlifedata.com/resource/pubmed/id/8410979

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1993-10-29
pubmed:abstractText
A series of tricyclic (nor-D) partial ergolines were synthesized via a highly convergent enantiospecific strategy, ultimately arising from a racemic tricyclic ketone. Michael addition to an acrylamide, followed by reductive methylation, afforded the key intermediate. Selective deprotection and oxidation provided the tricyclic ergoline. Vascular 5HT2 receptor interactions for the partial ergolines were dramatically reduced compared to the parent ergoline, amesergide, as determined in vivo by activation of a pressor response or blockade of 5HT-induced pressor responses in pithed rats. The desisopropyl tricyclic ergolines possessed some modest pressor activity that was unlikely to be related to 5HT2 receptor activation since these compounds did not inhibit the pressor response to serotonin. In contrast, the isopropyl tricyclic ergolines exhibited no agonist activity, but inhibited the pressor response to serotonin at 1 mg/kg i.v. The ergoline amesergide inhibited the pressor response to serotonin in doses of 0.01-0.1 mg/kg i.v. The homochiral isopropyl tricyclic ergoline was more potent as a 5HT2 receptor antagonist than the epimeric (unnatural stereochemistry) analogue. Thus, the isopropyl moiety on the indole nitrogen is important for vascular 5HT2 receptor affinity in the rat. Most importantly, these data suggest that conformational rigidity of the ergoline D-ring is required for optimal 5HT2 receptor interactions in the rat.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2671-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Amesergide and structurally related nor-D-ergolines: 5HT2 receptor interactions in the rat.
pubmed:affiliation
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
pubmed:publicationType
Journal Article, Comparative Study