Comparison of the inhibitory effects of cromakalim and pinacidil (potassium channel openers) with those of oxybutynin on stimulated guinea pig and rabbit detrusor muscle strips

To compare the inhibitory effects of a new group of smooth muscle relaxants, the potassium channel openers cromakalim and pinacidil, with those of oxybutynin on detrusor muscle stimulation in animals. Detrusor strips of guinea pigs (n=16) and rabbits (n=20) were mounted in organ bath for recording of isometric tension. α,β-methylene ATP (10^–7, 10^–6, 10^–5 M), carbachol (10^–6, 10^–5, 3×10^–5 , 5×10^–5 M) and transmural electrical-field stimulation (TES) were applied and concentration-response curves in the absence or presence of cromakalim (10^–6 , 10^–5 M), pinacidil (10^–5 , 5×10^–5 M) and oxybutynin (10^–5, 5×10^–5 M) were generated. All curves were displaced to the right in a concentration-dependent manner. The order of potency of inhibition was as follows: α,β-methylene ATP (pinacidil>oxybutynin>croma- kalim in guinea pigs; pinacidil>cromakalim>oxybutynin in rabbits); TES (pinacidil>cromakalim>oxybutynin in guinea pigs; cromakalim>oxybutynin>pinacidil in rabbits); carbachol (oxybutynin>pinacidil>cromakalim in guinea pigs; oxybutynin>cromakalim>pinacidil in rabbits). Cromakalim and pinacidil mainly inhibited purinergic-induced (α,β-methylene ATP and TES) detrusor contractions. Received: 9 November 2000 / Accepted: 25 November 2000