Actions of terodiline, its isomers and main metabolite on isolated detrusor muscle from rabbit and man.

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.