Linked Life Data

20182702

Source:http://linkedlifedata.com/resource/pubmed/id/20182702

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-4-29
pubmed:abstractText
The muscarinic receptor antagonist propiverine used for therapy of overactive bladder undergoes first pass metabolism, leading to several active metabolites, which affect muscarinic receptors and L-type Ca(2+) channels with different potencies. M-5, the major metabolite in blood, and M-6 can be synthesized as cis- and trans-isomers. We systematically investigated the pharmacodynamic profiles of the isomers on detrusor contractile function. In murine and porcine detrusor, the effects of the derivatives were examined on contractions induced by electric field stimulation (EFS), cumulatively increasing concentrations of carbachol or high KCl concentration. EFS contractions were concentration-dependently reduced by the M-5 and M-6 isomers although to a different extent. M-5(cis) was slightly more potent than M-5(trans), but the differences did not reach statistical significance. M-6(cis) was significantly more potent than M-6(trans). Responses to carbachol were antagonized by all compounds due to rightward shifts of the concentration-response curves, but only M-5(trans) also significantly reduced the maximum response. pK (B) values obtained with Schild plot analysis indicated slightly higher potency for M-6(cis) than M-6(trans). Ca(2+) influx-dependent contractions elicited by K(+) depolarization were less impaired by low concentrations of the M-6 isomers, but strongly suppressed by 100 microM of the M-5 isomers, suggesting an additional effect of the two M-5 isomers on Ca(2+) influx. All investigated isomers of M-5 and M-6 are biologically active in reducing detrusor contraction in animal tissue. While M-5( cis,) M-6(cis), and M-6(trans) possess surmountable or partially surmountable antagonistic properties at muscarinic receptors, M-5(trans) is a strong non-competitive antagonist. However, at higher concentration ranges, all four compounds seem to have additional effects on Ca(2+) influx.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1432-1912
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
381
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
329-38
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Anticholinergic effects of cis- and trans-isomers of two metabolites of propiverine.
pubmed:affiliation
Department of Urology, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetscherstrasse 74, 01307 Dresden, Germany. stefan.propping@uniklinikum-dresden.de
pubmed:publicationType
Journal Article, Comparative Study