Abstract To compare the inhibitory effects of a new group of smooth muscle relaxants, the potassium channel openers cromakalim and pinacidil, with those of oxybu- tynin on detrusor muscle stimulation in animals. Detru- sor strips of guinea pigs (n=16) and rabbits (n=20) were mounted in organ bath for recording of isometric ten- sion. 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 cromaka- lim (10 –6 , 10 –5 M), pinacidil (10 –5 , 5×10 –5 M) and oxy- butynin (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 fol- lows: 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 rab- bits); carbachol (oxybutynin>pinacidil>cromakalim in guinea pigs; oxybutynin>cromakalim>pinacidil in rab- bits). Cromakalim and pinacidil mainly inhibited purine- rgic-induced (α,β-methylene ATP and TES) detrusor contractions. Keywords Cromakalim · Detrusor muscle · Pinacidil · Potassium channel openers · Oxybutynin Introduction Detrusor instability (DI) is a common urological prob- lem that severely affects the quality of life of many women and men. As yet, the pathophysiology of the con- dition is incompletely understood and therefore the re- sults of available treatment including drug therapy are usually disappointing [2, 17]. Anticholinergic agents par- ticularly oxybutynin hydrochloride (OH) are usually considered the drugs of first choice because they reduce bladder contractions and associated symptoms in most patients [2, 23]. In many animal models and the isolated human bladder, however, these drugs only partially an- tagonize the response of the whole bladder smooth mus- cle to nerve stimulation and of bladder strips to field stimulation although they completely inhibit the re- sponse to exogenous cholinergic stimulation [6, 10, 18, 20, 22]. The most widely accepted explanation for this phenomenon is that a significant portion of neurotrans- mission involved in bladder contraction is non-adren- ergic, non-cholinergic [5]. A purinergic system releasing adenosine 5’-triphosphate (ATP) that acts on a subtype of purinoceptors called P2x seems to be the most likely mechanism [4, 5, 6, 10, 20]. Despite these experimental findings, the clinical importance of “atropine resistance” has never been established because of the marked differ- ences between the activation mechanisms of detrusor muscle in humans and animals and because in the nor- mal human bladder, the non-adrenergic, non-cholinergic component is small and sometimes difficult to demon- strate [23]. In the last two decades, a newly developed group of smooth muscle relaxants, the potassium channel openers (PCO), has stimulated interest for their potential thera- peutic role in DI [1, 2]. PCO decrease membrane excit- ability by acting on the ATP-sensitive potassium channel in the cell membrane to increase potassium efflux result- ing in membrane hyperpolarization and reduction of opening probability of ion channels involved in depolar- ization [3, 7, 8]. The best known and most clinically test- ed members of the group are pinacidil and cromakalim D.E.E. Rizk ( ✉ ) Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al-Ain, United Arab Emirates e-mail: rizk.diaa@uaeu.ac.ae Tel: 971-3-7672000, Fax: 971-3-7672067 K. Arafat · T. Y. El-Sharkawy Department of Physiology, United Arab Emirates University, Al-Ain Arch Gynecol Obstet (2001) 265:141–147 © Springer-Verlag 2001 ORIGINAL ARTICLE D.E.E. Rizk · K. Arafat · T.Y. El-Sharkawy 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 Received: 9 November 2000 / Accepted: 25 November 2000