Effects of three metabolites of propiverine on voltage-dependent L-type calcium currents in human atrial myocytes.
The non-selective muscarinic receptor antagonist propiverine impairs L-type Ca(2+) currents (I(Ca,L)) in human detrusor smooth muscle cells and atrial cardiomyocytes. Here, we have investigated the effects of three metabolites of propiverine on human cardiac I(Ca,L). Propiverine reduced I(Ca)(,L) with a -logIC(50) [M] value of 4.1, M-5 only showed minor effect on I(Ca)(,L) at high concentrations, M-6 did not influence I(Ca)(,L) at all. Like the parent compound M-14 also reduced I(Ca)(,L) (-logIC(50) [M]=4.6). We conclude, that propiverine and M-14 reduce cardiac I(Ca)(,L) at higher concentrations than in detrusor cells and therefore preferentially reduce I(Ca)(,L) in the urinary bladder than in the heart.
Wuest
Melinda
M
Department of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany. melinda.wuest@tu-dresden.de
Christ
Torsten
T
Hiller
Nicole
N
Braeter
Manfred
M
Ravens
Ursula
U
D001561:Benzilates / Q000493:pharmacokinetics / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002469:Cell Separation; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D015737:Nisoldipine / Q000494:pharmacology
D001561:Benzilates; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C015586:propiverine; D015737:Nisoldipine