Comparison of the effects of novel antimuscarinic drugs on human detrusor smooth muscle

Objective To evaluate the effects of tolterodine, vamicamide and temiverine , novel antimuscarinic drugs developed for the treatment of frequency and u rinary incontinence, on human detrusor smooth muscle. Materials and methods Specimens of human urinary bladder were obtained from 20 patients who underwent total cystectomy for malignant bladder tumour. U sing an organ-bath technique, the effects of various drugs on the contracti ons induced by carbachol, KCl, CaCl2 and electrical field stimulation in th e detrusor strips were investigated. Results Carbachol (0.001-10000 mu mol/L) caused concentration-dependent con tractions in human detrusor smooth muscles. Tolterodine (0.01-10 mu mol/L), vamicamide (0.01-10 mu mol/L), temiverine (0.01-1 mu mol/L) and atropine ( 0.001-1 mu mol/L) caused parallel shifts to the right of the concentration- response curves to carbachol. All slopes for the regression line of Schild plots were close to unity, and the rank order of pA(2) values was atro-pine = tolterodine > vamicamide > temiverine. Tolterodine, vamicamide and atrop ine did not inhibit the maximum contractile responses to carbachol, while t emiverine (10 mu mol/L) significantly inhibited the maximum contractions. T olterodine (0.001-1 mu mol/L) and vamicamide (0.01-10 mu mol/L) did not inh ibit the KCl- (80 mmol/L) and CaCl2-induced (5 mmol/L) contractions, while temiverine (0.01-10 mu mol/L) significantly inhibited the contractions. Ele ctrical field stimulation (2-60 Hz) caused frequency-dependent contractions in human detrusor smooth muscles, which were significantly inhibited by va rious drugs. In the presence of 1 mu mol/L atropine, tolterodine and vamica mide did not inhibit the contractions induced by electrical field stimulati on at all frequencies, while temiverine (10 mu mol/L) significantly inhibit ed the contractions. Conclusion Tolterodine and vamicamide inhibited contractions of human detru sor smooth muscles only through their antimuscarinic action, while temiveri ne had both antimuscarinic and calcium-antagonist actions. Furthermore, the se novel drugs have different efficacies and potencies for inhibiting human detrusor smooth muscle.