Importance of pharmacological and physicochemical properties for toleranceof antimuscarinic drugs in the treatment of detrusor instability and detrusor hyperreflexia - Chances for improvement of therapy

Background: Antimuscarinic side-effects are relatively frequent problems in oral pharmacotherapy of detrusor instability and neurogenic dysfunction of the urinary bladder. Results of recent clinical trials demonstrate differe nces in tolerance between antimuscarinic drugs. It is the purpose of this p aper to relate the available clinical data to the pharmacological and physi cochemical properties of the different antimuscarinic drugs, in order to di scuss the reasons for this enhanced tolerance and to make possible modes fo r improvement of antimuscarinic therapy plainly visible. Methods: Therefore , we reviewed the available literature using among others the computerized library systems Medline (National Library of Medicine, Bethesda, Maryland, USA) and Embase (Excerpta Medica, Amsterdam, the Netherlands). Differences in tolerance of oral antimuscarinic drugs may result from muscarine-recepto r selectivity, organ selectivity, and pharmacokinetic as well as physicoche mical properties. While the roles of m-receptor and organ selectivity need more detailed clarification, influences of differences in bioavailability a nd physicochemical properties on the tolerance of antimuscarinic drugs are more sufficiently investigated. Results: Generally, tolerance as well as ef ficacy of antimuscarinic drugs seem to be a complex result of a combination of various pharmacological properties distinguishing the individual substa nces. The enhancement of tolerance of propiverine hydrochloride, tolterodin e tartrate and trospium chloride compared to oxybutynin chloride seems to b e reached by different modes, from which the molecular structure - propiver ine and tolterodine are tertiary amines, trospium chloride possesses a quar ternary ammonium structure - may be of great importance. First investigatio ns with alternative transdermal and intravesical application routes show in teresting possibilities for further improvement of antimuscarinic therapy i n urological indications. Conclusion: In conclusion, from pharmacological a nd clinical data it becomes obvious that there are significant differences between antimuscarinic drugs, which are of clinical relevance and include p ossible starting points for the development of new drugs and application fo rms.