[Effects of propiverine hydrochloride (propiverine) on isolated rat and dog urinary bladder].
Propiverine is a drug for the treatment of incontinence and pollakiuria. The effects of propiverine on isolated rat and dog urinary bladder were investigated. At doses of 10(-6)-3 x 10(-5) M, propiverine caused both a rightward shift and inhibition of the maximum response in the acetylcholine (ACh) dose-response curve. The pA2 values for rat and dog urinary bladder were 5.97 and 6.62, respectively. At doses of 10(-5)-10(-5) M, propiverine also dose-dependently inhibited KCl (100 mM)-induced contractions. The IC50 values for rat and dog urinary bladder were 3.9 x 10(-6) M and 3.8 x 10(-6) M, respectively. The pA2 value and the IC50 value of terodiline for rat urinary bladder were 6.08 and 6.6 x 10(-6) M, respectively. In contrast, the pA2 value and the IC50 value of oxybutynin for rat urinary bladder were 7.69 and 4.5 x 10(-6) M, respectively, suggesting that oxybutynin exerts an anti-muscarinic effect at doses at which no discernible anti-KCl effect was observed, whereas propiverine and terodiline exerted both effects at the same doses. The inhibitory effect of drugs on the contraction induced by electrical field stimulation was tested. At a dose of 10(-7) g/ml, tetrodotoxin inhibited the contraction of rat and dog urinary bladder by 76.6% and 92.6%, respectively. Propiverine and verapamil dose-dependently inhibited the contractile response induced by electrical field stimulation at doses of 10(-5) M or more and 3 x 10(-6) M or more, respectively. At these concentrations, a marked anti-KCl effect of the drugs on smooth muscle was observed. On the other hand, atropine caused no inhibition of the contractile response in rat urinary bladder at a dose of 3 x 10(-5) M, and it inhibited the contraction in dog urinary bladder by 14.9% at a dose of 10(-5) M. These findings suggest that although propiverine exhibits both anti-muscarinic and anti-KCl effects in isolated rat and dog urinary bladder, the inhibitory effects of propiverine on the atropine-resistant part of contraction may be mainly due to its anti-KCl effect.
Kaneko
S
S
Pharmacology Research Laboratory, Taiho Pharmaceutical Co., Ltd, Tokushima, Japan.
Nakano
D
D
Ohara
M
M
Nishimori
T
T
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001561:Benzilates / Q000494:pharmacology*; D002082:Butylamines / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D011413:Propantheline / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects*; D014554:Urination / Q000187:drug effects; D014555:Urination Disorders / Q000188:drug therapy; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology
D001561:Benzilates; D002082:Butylamines; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D014665:Vasodilator Agents; D011413:Propantheline; C015586:propiverine; D011189:Potassium Chloride; C010637:terodiline; D001285:Atropine; D014700:Verapamil; C005419:oxybutynin; D000109:Acetylcholine