Anticholinergic and calcium antagonistic effects of terodiline in rabbit urinary bladder.
The effects of terodiline on contractions induced in isolated rabbit detrusor by carbachol and potassium, and by electrical field stimulation were investigated. Terodiline relaxed preparations contracted by carbachol and potassium and, when added 15 min before stimulation, decreased the contractile responses to these agents in a concentration-dependent way. Terodiline more effectively inhibited carbachol than potassium induced contractions. The "pure" calcium antagonist nifedipine had the opposite effect. Both atropine and terodiline caused a parallel shift to the right of the concentration-response curve to carbachol. The maximum contractile tension and slope were not affected, suggesting a competitive antimuscarinic effect within the concentration range used. Atropine was approximately 750 times more potent than terodiline. The maximum inhibitory effect of atropine and the calcium antagonist nimodipine on the electrically induced response were 40% and 69%, respectively. Terodiline caused complete inhibition of the response, as also did a combination of nimodipine and atropine. --The results suggest that terodiline in low concentrations has mainly an antimuscarinic action. To this, a calcium antagonistic effect is added at higher concentrations. The two-fold action of the drug makes it an effective inhibitor of bladder contraction, and an interesting tool for investigations of bladder contractility.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002082:Butylamines / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation; D009543:Nifedipine / Q000494:pharmacology; D010276:Parasympatholytics; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D001743:Urinary Bladder / Q000187:drug effects*
D002082:Butylamines; D010276:Parasympatholytics; C010637:terodiline; D001285:Atropine; D002217:Carbachol; D009543:Nifedipine; D011188:Potassium; D002118:Calcium