Linked Life Data

18683917

Source:http://linkedlifedata.com/resource/pubmed/id/18683917

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2008-9-5
pubmed:abstractText
The naturally occurring alkaloid, conessine (6), was discovered to bind to histamine H3 receptors in a radioligand-based high-throughput screen. Conessine displayed high affinity at both rat and human H3 receptors (pKi = 7.61 and 8.27) and generally high selectivity against other sites, including histamine receptors H1, H2, and H4. Conessine was found to efficiently penetrate the CNS and reach very high brain concentrations. Although the very slow CNS clearance and strong binding to adrenergic receptors discouraged focus on conessine itself for further development, its potency and novel steroid-based skeleton motivated further chemical investigation. Modification based on introducing diversity at the 3-nitrogen position generated a new series of H3 antagonists with higher in vitro potency, improved target selectivity, and more favorable drug-like properties. One optimized analogue (13c) was examined in detail and was found to be efficacious in animal behavioral model of cognition.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5423-30
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
The alkaloid conessine and analogues as potent histamine H3 receptor antagonists.
pubmed:affiliation
Department of Neuroscience Research, Global Pharmaceutical Research Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6123, USA. chen.zhao@abbott.com
pubmed:publicationType
Journal Article