Premium
Pharmacodynamics of propiverine and three of its main metabolites on detrusor contraction
Author(s) -
Wuest Melinda,
Hecht Juliane,
Christ Torsten,
Braeter Manfred,
Schoeberl Christian,
Hakenberg Oliver W,
Wirth Manfred P,
Ravens Ursula
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706244
Subject(s) - carbachol , atropine , chemistry , stimulation , contraction (grammar) , detrusor muscle , muscle contraction , endocrinology , urothelium , nifedipine , pharmacology , medicine , calcium , urinary bladder , biology , organic chemistry
1 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. 2 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. 3 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. 4 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. 5 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.British Journal of Pharmacology (2005) 145 , 608–619. doi: 10.1038/sj.bjp.0706244