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Author Wuest, Melinda ♦ Hecht, Juliane ♦ Christ, Torsten ♦ Manfred, Braeter ♦ Schoeberl, Christian ♦ Hakenberg, Oliver W. ♦ Wirth, Manfred P. ♦ Ravens, Ursula
Source PubMed Central
Content type Text
File Format PDF
Date Created 2005-05-09
Copyright Year ©2005
Language English
Difficulty Level Medium
Subject Domain (in DDC) Technology ♦ Medicine & health
Subject Keyword Pharmacology
Abstract Besides its antimuscarinic effects, propiverine may possess an additional mode of action. We compared the effects of propiverine, three of its metabolites (M-5, M-6, M-14) and atropine in human, pig and mouse urinary bladder preparations in order to elucidate the nature of a possible additional mode of action. Like the parent compound, M-5, M-6 and M-14 reduced to variable degrees the contractions elicited by electric field stimulation (EFS) of isolated, urothelium-denuded detrusor strips. In mouse the atropine-resistant and therefore the nonadrenergic, noncholinergic component of contractile response to EFS was reduced by M-5, M-14 and propiverine, but was hardly affected by M-6. Atropine, propiverine and M-6 significantly shifted the cumulative concentration–response curves for carbachol (CCh) to higher concentrations. Atropine and M-6 did not affect the maximum tension induced by CCh. Propiverine, M-5 and M-14 reduced the maximum CCh effect, suggesting at least one additional mode of action. This pattern of response was observed in all the three species, albeit with some differences in sensitivity to the various agents. In freshly isolated human detrusor smooth muscle cells, propiverine and M-14 inhibited the nifedipine-sensitive L-type calcium current (I Ca) in a concentration-dependent manner. In contrast, the effects of M-5 and M-6 on I Ca were insignificant in the concentration range examined. The investigated responses to propiverine and its metabolites suggest that impairment of maximum CCh-induced contractions is due to strong effect on I Ca and that this may be associated with the presence of the aliphatic side chain.
ISSN 00071188
Age Range above 22 year
Educational Use Research
Interactivity Type Expositive
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2005-07-01
Journal British Journal of Pharmacology
Volume Number 145
Issue Number 5
Page Count 12
Starting Page 608
Ending Page 619

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Source: PubMed Central