title: Actions of terodiline, its isomers and main metabolite on isolated detrusor muscle from rabbit and man.
abstract: The effects of racemic terodiline on isolated detrusor preparations from rabbit and man were compared with those of its (+)- and (-)-isomers, and with those of its main metabolite, parahydroxy-terodiline. Concentration-response (c-r) relations for carbachol and frequency-response relations for electrical stimulation were determined before and after addition of drugs. In preparations from both rabbit and man, all the drugs tested concentration-dependently shifted the c-r curve for carbachol to the right. (+)-Terodiline was more potent than (+/-)-terodiline, whereas (-)-terodiline and parahydroxy-terodiline were less potent. All drugs in concentrations greater than 10(-6) M had a non-competitive effect, depressing the maximum of the carbachol contraction. All drugs had a depressant effect on electrically evoked contractions. (+)-Terodiline was as effective (rabbit) or more effective (man) than (+/-)-terodiline, whereas (-)-terodiline and parahydroxy-terodiline were less effective. It is concluded that (+)-terodiline contributes to a main part of the detrusor effects of the racemate, and that part of this action is anticholinergic. Parahydroxy-terodiline had a profile of action similar to that of (+/-) terodiline, but its potency was low. Since it is present in plasma in low concentrations, its contribution to the clinical effects of terodiline is probably small. (+)-Terodiline may have a therapeutic potential.
authors.affiliation: Department of Clinical Pharmacology, University Hospital, Lund, Sweden.
authors.forename: K E
authors.initials: KE
authors.lastname: Andersson
authors.forename: B
authors.initials: B
authors.lastname: Ekström
authors.forename: A
authors.initials: A
authors.lastname: Mattiasson
mesh_terms: D000818:Animals; D002082:Butylamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011817:Rabbits; D013237:Stereoisomerism; D001743:Urinary Bladder / Q000187:drug effects*
chemical_list: D002082:Butylamines; C010637:terodiline