Experimental and clinical study of the effects of flavoxate in comparison with propantheline

ABSTRACT

In the present study the pharmacological effects of both flavoxate hydrochloride and propantheline bromide were studied experimentally on urinary bladder strips, intestinal smooth muscles, hearts and aortic strips isolated from rabbits. In-vivo experiments were also carried out to detect their effects on mean arterial blood pressure, heart rate and intraocular pressure of anaesthetized rabbits. In addition, antisecretory effects on basal gastric secretion in rats were investigated. Finally, both drugs were evaluated urodynamically in a clinical study on patients with cystitis. Each of flavoxate and propantheline elicited a significant concentration dependent spasmolytic effect on isolated urinary bladder strips and jejunal smooth muscles. Flavoxate was found to be more selective than propantheline on urinary bladder smooth muscle with potency ratio equal to 38.2. On the other hand, propantheline was found to exhibit a higher selectivity on isolated intestinal smooth muscle with potency ratio equal to 82.2. Comparing the smooth muscle relaxant activity of flavoxate and propantheline on the previous tissues, it was found that flavoxate activity was 237.4 times higher at the urinary bladder while propantheline activity was 13.2 times higher at jejunal smooth muscle. Flavoxate and propantheline displaced the Ach concentration response curves of the rabbit urinary bladder strips to the right. Propantheline and flavoxate produced competitive and weak anticholinergic activities with percentages of antagonistic actions about 83.3% and 33.3% respectively. The Ca [++] antagonistic activity of flavoxate was confirmed in the performed study on CaCl[2] concentration response curves on isolated urinary bladder strips depolarized with KCl, flavoxate produced competitive antagonism with the percentage of 76.5% while propantheline elicited non competitive Ca [++] antagonism with the percentage of 8.8%. Flavoxate also expressed its Ca[++] antagonistic activity on isolated rabbit hearts and aortic strips. Furthermore, in water cystometric recordings for patients with cystitis, flavoxate was more effective in increasing bladder capacity indicating its effect on micturition center, while bladder contractility was decreased more by propantheline denoting its higher antimuscarinic activity