Linked Life Data

17884104

Source:http://linkedlifedata.com/resource/pubmed/id/17884104

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2007-10-9
pubmed:abstractText
The use of combination drugs is very common in therapeutics as in the treatment of infectious diseases, cancer and heart failure but controversies about analysis of these interactions are frequent. The aim of the present work was to characterize the interaction between ouabain and 8-methoxy-3,9-dihydroxy coumestan (LQB93), a non-steroidal synthetic inhibitor of Na+,K+-ATPase, as well as the interaction between ouabain and ouabagenin, two cardiac glycosides sharing the same binding site. Inhibition of rat kidney Na+,K+-ATPase with increasing concentrations of the drugs alone or of mixtures of ouabain:ouabagenin and LQB93:ouabain in a fixed 1:4 ratio was performed. In other experiments, increasing concentrations of LQB93 (or ouabain) in the presence of a fixed concentration of ouabain (or ouabagenin) were used for determining the concentration pairs eliciting 50% inhibition in order to construct isobolograms. The mixture (experimental) curve for the ouabain:ouabagenin combination was superimposed on the additive (theoretical) curve indicating additivity, in accordance with the isobolographic analysis. On the other hand, the empirical curve for LQB93:ouabain (IC50=10.6 microM) was significantly shifted to the left in relation to the theoretical curve (IC50=30.7 microM) indicating synergism, further confirmed by the isobolographic analysis. As a conclusion, we show that the combination of a newly synthesized non-steroidal inhibitor and ouabain have a synergistic effect on Na+,K+-ATPase, further supporting a mechanism of inhibition different from ouabain. Present data also support the use of both the isobolograms and combination curves for the assessment of drug interactions occurring at the same molecular target, a situation poorly investigated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0024-3205
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1199-204
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Synergistic interaction between ouabain and 8-methoxy-3,9-dihydroxy coumestan, a non-steroidal synthetic inhibitor of Na+,K+-ATPase.
pubmed:affiliation
Departamento de Farmacologia Básica e Clínica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, RJ 21941 590, Brazil.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't