Responses of isolated normal human detrusor muscle to various spasmolytic drugs commonly used in the treatment of the overactive bladder

The spasmolytic activity of flavoxate (CAS 15301-69-6) and the anticholiner gic agents oxybutynin (CAS 5633-20-5), tolterodine (CAS 124937-51-5) and tr ospium chloride (CAS 10405-02-4), all of which are commonly utilized in the treatment of urinary incontinence, on muscarinic tension and electrically evoked contractions of isolated human detrusor smooth muscle strips was stu died using the organ bath technique. Within the concentration ranges tested (trospium chloride 10(-11)-10(-6) mol/l. flavoxate and oxybutynin 10(-9)-1 0(-5) mol/l, tolterodine 10(-10)-10(-5) mol/l), each drug caused a concentr ation-dependent relaxation of the tension elicited by muscarinic stimulatio n and dose-dependently attenuated the contractions induced by electrical fi eld stimulation (EFS). The effects of trospium chloride and tolterodine on carbachol-induced muscarinic tension were more pronounced than those of oxy butynin, while trospium chloride and oxybutynin were most effective in inhi biting the contractions induced by EFS. Flavoxate was significantly less ef fective than all other drugs tested. Regardless the individual drug concent rations needed for maximal efficacy, the potency of oxybutynin and navoxate to reverse muscarinic tension and attenuate EFS-evoked contractions was al most comparable while tolterodine and trospium chloride were more effective in relaxing the muscarinic tension of the detrusor strip preparations than causing inhibition of EFS-induced contractions. Our results again underlin e the ratio for the use of nortropane analogues (trospium chloride) and phe nyl-propylamine cresols (tolterodine) in the treatment of frequency, urgenc y and urge incontinence secondary to an overactive bladder.