Pharmacological effects of propiverine and its active metabolite, M-1, on isolated human urinary bladder smooth muscle, and on bladder contraction in rats.
OBJECTIVE
To investigate the effects of M-1, a major active metabolite of propiverine on the bladder.


METHODS
We have evaluated the effects of M-1 on the contractions induced by carbachol, KCl, CaCl(2), and electrical field stimulation (EFS) in human detrusor smooth muscles, and pelvic nerve stimulation-induced bladder contractions in rats. The effects of M-1 were also compared with the effects of propiverine and tolterodine.


RESULTS
Pretreatment with propiverine and tolterodine caused parallel shifts to the right of the concentration-response curves to carbachol. M-1 caused concentration-dependent reduction in the maximum contractile responses induced by carbachol. Although tolterodine did not inhibit the KCl- and CaCl(2)-induced contractions, M-1 and propiverine significantly inhibited these contractions. In the presence of atropine, M-1 and propiverine significantly inhibited the atropine resistant part of the contraction induced by EFS. On the other hand, tolterodine did not have significant inhibitory effects on atropine resistant contractions. Pelvic nerve stimulation induced bimodal phasic and tonic contractions in the rat bladder. M-1 mainly inhibited the phasic contraction. Tolterodine caused a significant inhibition in the tonic contraction, and propiverine had inhibitory effects on both contractions.


CONCLUSIONS
The present results suggest that M-1 has inhibitory effects on the bladder smooth muscles through calcium antagonistic action. It is possible that the clinical effects of propiverine on the human bladder are based not only on the action of propiverine itself but also on one of its active metabolites, M-1.
Sugiyama
Yutaka
Y
Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yoshida
Masaki
M
Masunaga
Koichi
K
Satoji
You
Y
Maeda
Yoshihiro
Y
Nagata
Takashi
T
Inadome
Akito
A
Ueda
Shoichi
S
D000368:Aged; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001561:Benzilates / Q000494:pharmacology*; D002217:Carbachol; D018679:Cholinergic Agonists; D003408:Cresols / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005260:Female; D006801:Humans; D023421:Models, Animal; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D010665:Phenylpropanolamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000068737:Tolterodine Tartrate; D001743:Urinary Bladder / Q000187:drug effects*
D001559:Benzhydryl Compounds; D001561:Benzilates; D018679:Cholinergic Agonists; D003408:Cresols; D003497:Cyclic N-Oxides; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; C113811:propiverine N-oxide; D010665:Phenylpropanolamine; C015586:propiverine; D000068737:Tolterodine Tartrate; D002217:Carbachol