Effects of a novel β3‐adrenoceptor agonist,AJ‐9677, on relaxation of the detrusor muscle: An in vitro study

Objectives: To examine the relaxant effects of AJ‐9677, a novel β₃‐adrenoceptor agonist, on the isolated rat, monkey and human detrusor muscle. Methods: The isolated detrusor strips of rats, monkeys and humans were mounted in organ baths containing Krebs solution. By the cumulative addition of β‐adrenoceptor agonists (isoproterenol, AJ‐9677, CL 316,243 and salbutamol in rats; isoproterenol, AJ‐9677 and CL 316,243 in monkeys and humans), concentration–relaxation curves were obtained. The maximal relaxation responses and pEC₅₀ values were calculated. In rats, concentration–relaxation curves to isoproterenol and AJ‐9677 were obtained in the presence and absence of propranolol or SR 59230A. Results: Isoproterenol, AJ‐9677, CL 316,243 and salbutamol induced concentration‐dependent relaxation in rats. The rank order of their relaxing potency in the rat detrusor muscle was AJ‐9677 > isoproterenol > CL 316,243 > salbutamol. Isoproterenol and AJ‐9677 also produced a concentration‐dependent relaxation with high potency in monkeys and humans, whilst CL 316,243 had low relaxing potency. According to the antagonist studies in rats, propranolol and SR 59230A caused a rightward shift of the concentration–relaxation curves to isoproterenol or AJ‐9677, respectively. Conclusions: AJ‐9677 has a high relaxant potency on the rat, monkey and human detrusor smooth muscle, and it may have the potential to treat overactive bladder.