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

Abstract

The spasmolytic activity of flavoxate (CAS 15301-69-6) and the anticholinergic agents oxybutynin (CAS 5633-20-5), tolterodine (CAS 124937-51-5) and trospium 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 studied using the organ bath technique. Within the concentration ranges tested (trospium chloride 10(-11)-10(-6) mol/l, flavoxate and oxybutynin 10(-9)-10(-5) mol/l, tolterodine 10(-10)-10(-5) mol/l), each drug caused a concentration-dependent relaxation of the tension elicited by muscarinic stimulation and dose-dependently attenuated the contractions induced by electrical field stimulation (EFS). The effects of trospium chloride and tolterodine on carbachol-induced muscarinic tension were more pronounced than those of oxybutynin, while trospium chloride and oxybutynin were most effective in inhibiting the contractions induced by EFS. Flavoxate was significantly less effective than all other drugs tested. Regardless the individual drug concentrations needed for maximal efficacy, the potency of oxybutynin and flavoxate to reverse muscarinic tension and attenuate EFS-evoked contractions was almost 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 underline the ratio for the use of nortropane analogues (trospium chloride) and phenylpropylamine cresols (tolterodine) in the treatment of frequency, urgency and urge incontinence secondary to an overactive bladder.

• Authors: S Uckert, C G Stief, K P Odenthal, M C Truss, B Lietz, U Jonas
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 50 Issue 5 Pg. 456-60 (May 2000) ISSN: 0004-4172 [Print] Germany
• PMID: 10858873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Muscarinic Agonists
• Parasympatholytics
• Carbachol

Topics

• Carbachol (pharmacology)
• Electric Stimulation
• Humans
• In Vitro Techniques
• Muscarinic Agonists (pharmacology)
• Muscle Contraction (drug effects, physiology)
• Muscle, Smooth (drug effects, physiology)
• Parasympatholytics (pharmacology, therapeutic use)
• Urinary Bladder, Neurogenic (drug therapy)