TRK-380, a Novel Selective Human β3-Adrenoceptor Agonist, Ameliorates Formalin-induced Pollakiuria in Rats and Carbachol-induced Bladder Contraction in Dogs

摘要: Objective To investigate the effects of TRK-380, a selective β 3 -adrenoceptor (β -AR) agonist, on voiding behavior in rats with pollakiuria and carbachol (CCh)-induced bladder contraction dogs. Methods The female Sprague Dawley was recorded continuously balance. Rats were intravesically pretreated 2.5% formalin under isoflurane anesthesia. next day, effect TRK-380 (7.5-30 mg/kg, orally) or tolterodine, an antimuscarinic drug (3.75-15 orally), frequency evaluated. In another experiment, male beagle dogs anesthetized pentobarbital, CCh (3 μg/kg, intravenously) administered to them, (0.1 0.3 μg/kg/minute, intravenously infusion) CCh-induced Results treated showed significant increase compared sham group, it significantly dose-dependently suppressed by at doses ≥15 mg/kg. contrast, tolterodine did not lead to change even highest dose. dogs, TRK-380; plasma concentration required for 30% suppression (30% relaxation) 4.90 ng/mL. Conclusion This study indicated that ameliorated pollakiuria, which resistant drug, also induced cholinergic stimulation whose relaxation is known be predominantly mediated -ARs, as humans. These data strengthen therapeutic potential -AR treatment overactive bladder.