Linked Life Data

7861407

Source:http://linkedlifedata.com/resource/pubmed/id/7861407

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-3-21
pubmed:abstractText
Small conductance Ca(2+)-activated K+ (SKCa) channels occur in many cells but have been relatively little studied. Dequalinium, a bis-quinolinium compound, has recently been shown to be the most potent nonpeptidic blocker of this K+ channel subtype. This paper examines the importance of the quinolinium rings for blocking activity. Analogues of dequalinium were synthesised in which one quinolinium group was removed (1 and 2) or replaced by a triethylammonium group (3). They have been assayed in vitro for their ability to block the after-hyperpolarization (mediated by the opening of SKCa channels) that follows the action potential in rat sympathetic neurones. The compound having one quinolinium and one triethylammonium group (3) showed reduced activity, and it is suggested that the stronger binding to the channel of the quinolinium relative to the triethylammonium group may be related to differences in their electrostatic potential energy maps. Two monoquaternary compounds (1 and 2) were tested, but they exhibited a different pharmacological profile that did not allow definite conclusions to be drawn concerning their potency as blockers of the SKCa channel. Replacement of both quinolinium groups by pyridinium, acridinium, isoquinolinium, or benzimidazolium reduced but did not abolish activity. These results show that compounds having a number of different heterocyclic cations are capable of blocking the SKCa channel. However, among the heterocycles studied, quinoline is optimal. Furthermore, charge delocalization seems to be important: the higher the degree of delocalization the more potent the compound.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
595-606
pubmed:dateRevised
2009-9-29
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Synthesis and structure-activity relationships of dequalinium analogues as K+ channel blockers. Investigations on the role of the charged heterocycle.
pubmed:affiliation
Department of Chemistry, University College London, U.K.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't